{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:51:41Z","timestamp":1783525901161,"version":"3.55.0"},"reference-count":118,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Genetic diseases in Tunisia are a real public health problem given their chronicity and the lack of knowledge concerning their prevalence and etiology, and the high rates of consanguinity. Hence, we performed systematic reviews of the literature in order to provide a more recent spectrum of these disorders and to expose the challenges that still exist to tackle these kinds of diseases. A manual textual data mining was conducted using MeSH and PubMed databases. Collected data were classified according to the CIM-10 classification and the transmission mode. The spectrum of these diseases is estimated to be 589 entities. This suggests remarkable progress through the development of biomedical health research activities and building capacities. Sixty percent of the reported disorders are autosomal recessive, which could be explained by the high prevalence of endogamous mating. Congenital malformations (29.54%) are the major disease group, followed by metabolic diseases (22%). Sixty percent of the genetic diseases have a known molecular etiology. We also reported additional cases of comorbidity that seem to be a common phenomenon in our population. We also noticed that epidemiological data are scarce. Newborn and carrier screening was only limited to pilot projects for a few genetic diseases. Collected data are being integrated into a database under construction that will be a valuable decision-making tool. This study provides the current situation of genetic diseases in Tunisia and highlights their particularities. Early detection of the disease is important to initiate critical intervention and to reduce morbidity and mortality.<\/jats:p>","DOI":"10.3390\/genes12111820","type":"journal-article","created":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T08:29:17Z","timestamp":1637310557000},"page":"1820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Spectrum of Genetic Diseases in Tunisia: Current Situation and Main Milestones Achieved"],"prefix":"10.3390","volume":"12","author":[{"given":"Nessrine","family":"Mezzi","sequence":"first","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"},{"name":"Department of Biology, Faculty of Sciences of Bizerte, Universit\u00e9 Tunis Carthage, Jarzouna 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4547-0180","authenticated-orcid":false,"given":"Olfa","family":"Messaoud","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Mkaouar","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Zitouna","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Romdhane","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaith","family":"Abdessalem","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4656-2661","authenticated-orcid":false,"given":"Cherine","family":"Charfeddine","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"},{"name":"High Institute of Biotechnology of Sidi Thabet, Biotechpole of Sidi Thabet, University of Manouba, Ariana 2080, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faouzi","family":"Maazoul","sequence":"additional","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Ouerteni","sequence":"additional","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosr","family":"Hamdi","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"},{"name":"Laboratory of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anissa","family":"Zaouak","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Research Unit Genodermatosis and Cancer LR12SP03, Habib Thameur Hospital, Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridha","family":"Mrad","sequence":"additional","affiliation":[{"name":"Department of Congenital and Hereditary Diseases, Charles Nicolle Hospital, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-5525","authenticated-orcid":false,"given":"Sonia","family":"Abdelhak","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-7272","authenticated-orcid":false,"given":"Lilia","family":"Romdhane","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis 1002, Tunisia"},{"name":"Department of Biology, Faculty of Sciences of Bizerte, Universit\u00e9 Tunis Carthage, Jarzouna 7021, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/ajmg.a.61124","article-title":"The burden of rare diseases","volume":"179","author":"Ferreira","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1001\/jama.2019.0290","article-title":"The Orphan Drug Act Revisited","volume":"321","author":"Thomas","year":"2019","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.jval.2015.05.008","article-title":"Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group","volume":"18","author":"Richter","year":"2015","journal-title":"Value Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e000794","DOI":"10.1136\/rmdopen-2018-000794","article-title":"Rare diseases under different levels of economic analysis: Current activities, challenges and perspectives","volume":"4","author":"Palla","year":"2018","journal-title":"RMD Open"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41368-018-0041-y","article-title":"Dental-craniofacial manifestation and treatment of rare diseases","volume":"11","author":"Luo","year":"2019","journal-title":"Int. J. Oral. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1136\/bmj.38982.704931.AE","article-title":"Genetic disorders in the Arab world","volume":"333","year":"2006","journal-title":"Br. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1146\/annurev-genom-083118-014954","article-title":"Consanguinity and inbreeding in health and disease in North African populations","volume":"20","author":"Romdhane","year":"2019","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.gene.2016.07.007","article-title":"The Arab genome: Health and wealth","volume":"592","author":"Zayed","year":"2016","journal-title":"Gene"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1742-4755-6-17","article-title":"Consanguinity and reproductive health among Arabs","volume":"6","author":"Tadmouri","year":"2009","journal-title":"J. Reprod. Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/1750-1172-7-52","article-title":"Founder mutations in Tunisia: Implications for diagnosis in North Africa and Middle East","volume":"7","author":"Romdhane","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1353\/hub.2010.a394730","article-title":"Ancient local evolution of African mtDNA haplogroups in Tunisian Berber populations","volume":"82","author":"Frigi","year":"2010","journal-title":"Hum. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"593","DOI":"10.3109\/19401736.2013.879649","article-title":"Phylogeny and genetic structure of Tunisians and their position within Mediterranean populations","volume":"26","author":"Kefi","year":"2015","journal-title":"Mitochondrial DNA"},{"key":"ref_13","unstructured":"Mughal, M. (2013). In Tunisia, in Native Peoples of the World: An Encyclopedia of Groups, Cultures, and Contemporary Issues, Routledge."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hajjej, A., Almawi, W.Y., Hattab, L., El-Gaaied, A., and Hmida, S. (2015). HLA Class I and Class II Alleles and Haplotypes Confirm the Berber Origin of the Present Day Tunisian Population. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0136909"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/s00038-014-0616-0","article-title":"Health system challenges of NCDs in Tunisia","volume":"60","author":"Tlili","year":"2015","journal-title":"Int. J. Public Health"},{"key":"ref_16","first-page":"335","article-title":"Tunisia: \u201cGood Practice\u201d in expanding health care coverage: Lessons from reforms in a country in transition","volume":"Volume 20","author":"Arfa","year":"2008","journal-title":"Good Practices in Health Financing Lessons from Reforms in Low-and Middle-Income Countries"},{"key":"ref_17","unstructured":"Ben Romdhane, H., Husseini, A., and Jabbour, S. (2012). Non-Communicable Diseases\u2014II: Focus on Cardiovascular Diseases, Cambridge University Press."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Atek, M., Traissac, P., El Ati, J., Laid, Y., Aounallah-Skhiri, H., Eymard-Duvernay, S., M\u00e9zim\u00e8che, N., Bougatef, S., B\u00e9ji, C., and Boutekdjiret, L. (2013). Obesity and association with area of residence, gender and socio-economic factors in Algerian and Tunisian adults. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075640"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12687-012-0128-7","article-title":"Consanguinity, endogamy, and genetic disorders in Tunisia","volume":"4","author":"Bouafif","year":"2013","journal-title":"J. Community Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1159\/000362167","article-title":"Specific aspects of consanguinity: Some examples from the Tunisian population","volume":"77","author":"Romdhane","year":"2014","journal-title":"J. Human Hered."},{"key":"ref_21","unstructured":"Zakaria, D. (1999). Etude de L\u2019endogamie D\u2019origine R\u00e9gionale, de la Distribution de la Consanguinit\u00e9 Apparente et du Comportement Interg\u00e9n\u00e9rationnel Dans le Choix Matrimonial en Tunisie. Int\u00e9r\u00eat des Noms de Famille et de L\u2019isonymie Maritale. [Ph.D. Thesis, Faculty of Science, University of Tunis]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ajhb.22764","article-title":"Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia","volume":"28","author":"Hsouna","year":"2016","journal-title":"Am. J. Hum. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/ajmg.a.33771","article-title":"Genetic diseases in the Tunisian population","volume":"155","author":"Romdhane","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1111\/j.1399-0004.2010.01403.x","article-title":"Only two mutations detected in 15 Tunisian patients with 11beta-hydroxylase deficiency: The p.Q356X and the novel p.G379V","volume":"78","author":"Kharrat","year":"2010","journal-title":"Clin. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1159\/000346680","article-title":"Molecular characterization of X-linked adrenoleukodystrophy in a Tunisian family: Identification of a novel missense mutation in the ABCD1 gene","volume":"12","author":"Kallabi","year":"2013","journal-title":"Neurodegener. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.ejmg.2016.08.004","article-title":"Long-term clinical follow-up and molecular testing for diagnosis of the first Tunisian family with Alstrom syndrome","volume":"59","author":"Chakroun","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1111\/jdv.12279","article-title":"Chromosomal instability associated with a novel BLM frameshift mutation (c. 1980-1982delAA) in two unrelated Tunisian families with Bloom syndrome","volume":"28","author":"Salah","year":"2014","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/1746-1596-7-93","article-title":"First report of molecular diagnosis of Tunisian. hemophiliacs A: Identification of 8 novel. causative mutations","volume":"7","author":"Kek","year":"2012","journal-title":"Diagn. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.patbio.2012.03.006","article-title":"Molecular diagnosis of Gaucher disease in Tunisia","volume":"61","author":"Cherif","year":"2012","journal-title":"Pathol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1159\/000314076","article-title":"A novel LAMA3 mutation in a newborn with junctional epidermolysis bullosa herlitz type","volume":"99","author":"Mazzucchelli","year":"2011","journal-title":"Neonatology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jns.2011.02.011","article-title":"A novel exon 3 mutation in a Tunisian patient with Lafora\u2019s disease","volume":"304","author":"Khiari","year":"2011","journal-title":"J. Neurol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e193","DOI":"10.1097\/MPH.0000000000001192","article-title":"A Novel Mutation c.153 C > A in a Tunisian Girl with Wolman Disease and Unusual Presentation: Hemophagocytic Lymphohistiocytosis","volume":"41","author":"Tinsa","year":"2018","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.gene.2012.12.097","article-title":"Molecular characterization of maple syrup urine disease patients from Tunisia","volume":"517","author":"Jaafar","year":"2013","journal-title":"Gene"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/ng.594","article-title":"Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes","volume":"42","author":"Valente","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3109\/19401736.2012.748045","article-title":"Screening of mitochondrial mutations in Tunisian patients with mitochondrial disorders: An overview study","volume":"24","author":"Chamkha","year":"2013","journal-title":"Mitochondrial DNA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.gene.2013.06.045","article-title":"Posterior microphthalmia and nanophthalmia in Tunisia caused by a founder c.1059_1066insC mutation of the PRSS56 gene","volume":"528","author":"Said","year":"2013","journal-title":"Gene"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"5755","DOI":"10.1007\/s11033-020-05643-9","article-title":"Novel splicing dysferlin mutation causing myopathy with intra-familial heterogeneity","volume":"47","author":"Rekik","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Chkioua, L., Grissa, O., Leban, N., Gribaa, M., Boudabous, H., Turkia, H.B., Ferchichi, S., Tebib, N., and Laradi, S. (2020). The mutational spectrum of hunter syndrome reveals correlation between biochemical and clinical profiles in Tunisian patients. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-01051-9"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2326","DOI":"10.1016\/j.cca.2011.08.032","article-title":"Molecular characterization of MPS IIIA, MPS IIIB and MPS IIIC in Tunisian patients","volume":"412","author":"Ouesleti","year":"2011","journal-title":"Clin. Chim. Acta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.mgene.2015.07.003","article-title":"Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene","volume":"5","author":"Chkioua","year":"2015","journal-title":"Meta Gene"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/ng.2444","article-title":"Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma","volume":"44","author":"Pohler","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1111\/cge.12616","article-title":"Comorbidity in the Tunisian population","volume":"89","author":"Romdhane","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s10067-011-1923-y","article-title":"Association of amyotrophic lateral sclerosis and Behcet\u2019s disease: Is there a relationship? A multi-national case series","volume":"31","author":"Mrabet","year":"2012","journal-title":"Clin. Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1111\/ijd.14452","article-title":"A Tunisian family with a novel mutation in the gene CYP4F22 for lamellar ichthyosis and co-occurrence of hearing loss in a child due to mutation in the SLC26A4 gene","volume":"58","author":"Sayeb","year":"2019","journal-title":"Int. Soc. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ghedira, N., Lagarde, A., Ben Ameur, K., Elouej, S., Sakka, R., Kerkeni, E., Chioukh, F.Z., Olschwang, S., Desvignes, J.P., and Abdelhak, S. (2018). Clinical profile of comorbidity of rare diseases in a Tunisian patient: A case report associating incontinentia pigmenti and Noonan syndrome. BMC Pediatr., 18.","DOI":"10.1186\/s12887-018-1259-8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jdiacomp.2016.06.028","article-title":"Whole mitochondrial genome screening of a family with maternally inherited diabetes and deafness (MIDD) associated with retinopathy: A putative haplotype associated to MIDD and a novel MT-CO2 m.8241T>G mutation","volume":"31","author":"Tabebi","year":"2017","journal-title":"J. Diabetes Complicat."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.11604\/pamj.2020.36.367.25116","article-title":"Systemic lupus erythematosus, antiphospholipid syndrome and Hashimoto thyroiditis occurring in a patient with Niemann-Pick disease: A second case","volume":"36","author":"Baya","year":"2020","journal-title":"Pan Afr. Med. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1186\/s13023-019-1095-4","article-title":"Thyroid involvement in Chanarin-Dorfman syndrome in adults in the largest series of patients carrying the same founder mutation in ABHD5 gene","volume":"14","author":"Louhichi","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s10038-019-0711-4","article-title":"Identification of a CDH12 potential candidate genetic variant. for an autosomal dominant form of transgrediens and progrediens palmoplantar keratoderma in a Tunisian family","volume":"65","author":"Charfeddine","year":"2020","journal-title":"J. Hum. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s12031-018-1167-2","article-title":"A Novel SYNJ1 Mutation in a Tunisian Family with Juvenile Parkinson\u2019s Disease Associated with Epilepsy","volume":"66","author":"Sakka","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_51","first-page":"189","article-title":"Incidence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Tunisian populations","volume":"31","author":"Blibech","year":"1989","journal-title":"Nouv. Rev. Fr. d\u2019H\u00e9matol."},{"key":"ref_52","first-page":"e2009005","article-title":"Evolution of hemoglobinopathy prevention in Africa: Results, problems and prospect","volume":"1","author":"Fattoum","year":"2009","journal-title":"Mediterr. J. Hematol. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1212\/WNL.41.9.1385","article-title":"The Libyan Creutzfeldt-Jakob disease focus in Israel: An epidemiologic evaluation","volume":"41","author":"Miriam","year":"1991","journal-title":"Neurology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"664","DOI":"10.4314\/ahs.v18i3.24","article-title":"Cystic fibrosis in Tunisian children: A review of 32 children","volume":"18","author":"Boussetta","year":"2018","journal-title":"Afr. Health Sci."},{"key":"ref_55","first-page":"623","article-title":"Atopic dermatitis in Tunisia: Epidemiological and clinical aspects","volume":"128","author":"Kharfi","year":"2001","journal-title":"Ann. Dermatol. Venereol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00403-013-1421-y","article-title":"Mutational founder effect in recessive dystrophic epidermolysis bullosa families from Southern Tunisia","volume":"306","author":"Brick","year":"2014","journal-title":"Arch. Dermatol. Res."},{"key":"ref_57","first-page":"19","article-title":"The exfoliation syndrome in Tunisia","volume":"68","author":"Ayed","year":"1990","journal-title":"Tunis. Med."},{"key":"ref_58","unstructured":"Ben Abdallah, M., and Zehani, S. (2004). Registre des Cancers Nord.-Tunisie 1995\u20131998, Institut Salah Azaiez."},{"key":"ref_59","first-page":"1200","article-title":"Fanconi disease: Study of 43 cases in Southern Tunisia","volume":"5","author":"Frikha","year":"1998","journal-title":"Arch. Pediatr. Organe Off. Soc. Fr. Pediatr."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/0021-9150(93)90186-X","article-title":"Phenotypic expression of familial hypercholesterolaemia in central and southern Tunisia","volume":"104","author":"Slimane","year":"1993","journal-title":"Atherosclerosis"},{"key":"ref_61","first-page":"782","article-title":"Incidence of mucopolysaccharidoses in Tunisia","volume":"87","author":"Turkia","year":"2009","journal-title":"Tunis. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1055\/s-0040-1712489","article-title":"Nonketotic hyperglycinemia in tunisia. Report upon a series of 69 patients","volume":"51","author":"Nasrallah","year":"2020","journal-title":"Neuropediatrics"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1515\/jpem-2018-0151","article-title":"A lower energetic, protein and uncooked cornstarch intake is associated with a more severe outcome in glycogen storage disease type III: An observational study of 50 patients","volume":"31","author":"Chehida","year":"2018","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_64","first-page":"100","article-title":"Les mucopolysaccharidoses (MPS) sont des maladies de surcharge lysosomiale","volume":"59","author":"Laradi","year":"2001","journal-title":"Ann. Biol. Clin."},{"key":"ref_65","first-page":"1040","article-title":"Mild and severe muscular dystrophy caused by a single gamma-sarcoglycan mutation","volume":"59","author":"McNally","year":"1996","journal-title":"Am. J. Hum. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s10689-008-9215-7","article-title":"Identification and characterization of a novel MLH1 genomic rearrangement as the cause of HNPCC in a Tunisian family: Evidence for a homologous Alu-mediated recombination","volume":"8","author":"Moussa","year":"2009","journal-title":"Fam. Cancer"},{"key":"ref_67","first-page":"62","article-title":"Selective vitamin B12 malabsorption with proteinuria in Israel. Clinical and genetic aspects","volume":"5","author":"Feinstein","year":"1969","journal-title":"Isr. J. Med. Sci."},{"key":"ref_68","first-page":"3","article-title":"Les maladies h\u00e9r\u00e9ditaires du m\u00e9tabolisme en Tunisie: D\u00e9fis, acquis, espoirs","volume":"5","author":"Dridi","year":"2015","journal-title":"Arch. Pediatr. Organe Off. Soc. Fr. Pediatr."},{"key":"ref_69","first-page":"316286","article-title":"Further evidence of mutational heterogeneity of the XPC gene in Tunisian families: A spectrum of private and ethnic specific mutations","volume":"2013","author":"Jerbi","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/ijlh.12457","article-title":"Prenatal diagnosis of hemoglobinopathies in Tunisia: An 18 years of experience","volume":"38","author":"Ouali","year":"2016","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1556\/APhysiol.101.2014.013","article-title":"Preliminary study of haplotypes linked to the rare cystic fibrosis E1104X mutation","volume":"102","author":"Oueslati","year":"2015","journal-title":"Acta Physiol. Hung."},{"key":"ref_72","first-page":"643","article-title":"Early hearning screening by otoacoustic emissions and auditory brain stem response in Nabeul","volume":"91","author":"Abed","year":"2013","journal-title":"Tunis. Med."},{"key":"ref_73","first-page":"69","article-title":"Neonatal screening of G6PD deficiency in Tunisia","volume":"87","author":"Guellouz","year":"2010","journal-title":"Arch. L\u2019Inst. Pasteur Tunis"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"49","DOI":"10.5144\/0256-4947.2012.49","article-title":"A lower-cost protocol for sickle cell disease neonatal screening in Tunisia","volume":"32","author":"Hajer","year":"2012","journal-title":"Ann. Saudi Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.siny.2015.07.002","article-title":"Global burden of genetic disease and the role of genetic screening","volume":"20","author":"Verma","year":"2015","journal-title":"Semin. Fetal. Neonatal. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00439-019-02043-3","article-title":"Autosomal recessive diseases among the Israeli Arabs","volume":"138","author":"Zlotogora","year":"2019","journal-title":"Hum. Genet."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s00403-011-1190-4","article-title":"Severe phenotypes in two Tunisian families with novel XPA mutations: Evidence for a correlation between mutation location and disease severity","volume":"304","author":"Messaoud","year":"2012","journal-title":"Arch. Dermatol. Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00439-014-1418-4","article-title":"Genome-wide copy number variation study and gene expression analysis identify ABI3BP as a susceptibility gene for Kashin\u2013Beck disease","volume":"133","author":"Zhang","year":"2014","journal-title":"J. Hum. Genet."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1007\/s00439-017-1821-8","article-title":"The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes","volume":"136","author":"Monies","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000505886","article-title":"Rapid Identification of Biallelic SPTB Mutation in a Neonate with Severe Congenital Hemolytic Anemia and Liver Failure","volume":"11","author":"Richmond","year":"2020","journal-title":"Mol. Syndr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1080\/13816810.2019.1639202","article-title":"Granular type I corneal dystrophy in a large consanguineous Tunisian family with homozygous p.R124S mutation in the TGFBI gene","volume":"40","author":"Bouyacoub","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1007\/s11033-011-0990-0","article-title":"A novel CASR mutation in a Tunisian FHH\/NSHPT family associated with a mental retardation","volume":"39","author":"Sfar","year":"2012","journal-title":"Mol. Biol. Rep."},{"key":"ref_83","unstructured":"John, J.N., Sid, E., and Zhu, Q. (November, January 30). Recurrent Neural Networks to Automatically Identify Rare Disease Epidemiologic Studies from PubMed. Proceedings of the AMIA Annual Symposium Proceedings, San Diego, CA, USA."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13023-019-1088-3","article-title":"The DM-scope registry: A rare disease innovative framework bridging the gap between research and medical care","volume":"14","author":"Dogan","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1080\/03007995.2016.1198756","article-title":"An Arab registry for type 1 diabetes: Global benefits for type 1 diabetes patients","volume":"32","author":"Zayed","year":"2016","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_86","first-page":"3","article-title":"Regional registry of bleeding disorders in Tunisia","volume":"1","author":"Elmahmoudi","year":"2012","journal-title":"J. Haemoph."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13039-018-0412-2","article-title":"VIII World Rett Syndrome Congress & Symposium of rare diseases, Kazan, Russia","volume":"11","author":"Iourov","year":"2018","journal-title":"Mol. Cytogenet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.arcped.2015.12.004","article-title":"Burkitt lymphoma in a child with Bloom syndrome","volume":"23","author":"Ayed","year":"2016","journal-title":"Arch. P\u00e9diatr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.ijporl.2013.06.015","article-title":"A novel frameshift mutation (c. 405delC) in the GJB2 gene associated with autosomal recessive hearing loss in two Tunisian families","volume":"77","author":"Riahi","year":"2013","journal-title":"Int. J. Pediatr. Otorhinolaryngol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2013.04.078","article-title":"Update of the spectrum of GJB2 gene mutations in Tunisian families with autosomal recessive nonsyndromic hearing loss","volume":"525","author":"Riahi","year":"2013","journal-title":"Gene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/joim.12314","article-title":"Novel personalized therapies for cystic fibrosis: Treating the basic defect in all patients","volume":"277","author":"Amaral","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.2147\/DDDT.S153719","article-title":"Lumacaftor-ivacaftor in the treatment of cystic fibrosis: Design, development and place in therapy","volume":"13","author":"Connett","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"L364","DOI":"10.1152\/ajplung.00134.2016","article-title":"Personalized medicine in cystic fibrosis: Genistein supplementation as a treatment option for patients with a rare S1045Y-CFTR mutation","volume":"311","author":"Arora","year":"2016","journal-title":"Am. J. Physiol.\u2013Lung Cell. Mol. Physiol."},{"key":"ref_94","first-page":"627","article-title":"Molecular epidemiology of cystic fibrosis in Tunisia","volume":"63","author":"Messaoud","year":"2005","journal-title":"Ann. Biol. Clin."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12931-016-0326-7","article-title":"c. 3623G> A mutation encodes a CFTR protein with impaired channel function","volume":"17","author":"Zhang","year":"2016","journal-title":"Respir. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1089\/gtmb.2013.0326","article-title":"Carrier frequency of the c.525delT mutation in the SGCG gene and estimated prevalence of limb girdle muscular dystrophy type 2C among the Moroccan population","volume":"18","author":"Ratbi","year":"2014","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1089\/gte.2008.0061","article-title":"Molecular prenatal diagnosis of muscular dystrophies in Tunisia and postnatal follow-up role","volume":"12","author":"Siala","year":"2008","journal-title":"Genet. Test."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/brain\/awr342","article-title":"A phase I trial of adeno-associated virus serotype 1-\u03b3-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C","volume":"135","author":"Herson","year":"2012","journal-title":"Brain"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"674965","DOI":"10.3389\/fonc.2021.674965","article-title":"Identification of Eleven Novel BRCA Mutations in Tunisia: Impact on the Clinical Management of BRCA Related Cancers","volume":"11","author":"Hamdi","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1001\/jamapediatrics.2014.2465","article-title":"Universal state newborn screening programs can reduce health disparities","volume":"169","author":"Brosco","year":"2015","journal-title":"JAMA Pediatr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"100496","DOI":"10.1016\/j.ssmph.2019.100496","article-title":"Inequities in newborn screening: Race and the role of medicaid","volume":"9","year":"2019","journal-title":"SSM\u2014Popul. Health"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/gim.2013.177","article-title":"Developing a public health-tracking system for follow-up of newborn screening metabolic conditions: A four-state pilot project structure and initial findings","volume":"16","author":"Hinton","year":"2014","journal-title":"Genet. Med."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Urv, T.K., and Parisi, M.A. (2017). Newborn Screening: Beyond the Spot. Rare Diseases Epidemiology: Update Overview, Springer.","DOI":"10.1007\/978-3-319-67144-4_19"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e35","DOI":"10.1097\/AOG.0000000000001951","article-title":"Carrier screening in the age of genomic medicine: ACOG committee opinion, number 690","volume":"129","author":"Romero","year":"2017","journal-title":"Obs. Gynecol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1038\/s41436-019-0466-5","article-title":"A data-driven evaluation of the size and content of expanded carrier screening panels","volume":"21","author":"Svenson","year":"2019","journal-title":"Genet. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1097\/GIM.0b013e3181ab2277","article-title":"Conference report: Second conference of the Middle East and North Africa newborn screening initiative: Partnerships for sustainable newborn screening infrastructure and research opportunities","volume":"11","author":"Krotoski","year":"2009","journal-title":"Genet. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1016\/S0140-6736(06)68406-7","article-title":"Consanguinity: Implications for practice, research, and policy","volume":"367","author":"Teebi","year":"2006","journal-title":"J. Lancet"},{"key":"ref_108","first-page":"688","article-title":"Health screening strategies in Maghreb countries: Situation Analysis and perspectives","volume":"96","author":"Hsairi","year":"2018","journal-title":"Tunis. Med."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"703","DOI":"10.15537\/smj.2020.7.25147","article-title":"Incidence of newborn screening disorders among 56632 infants in Central Saudi Arabia. A 6-year study","volume":"41","author":"Mohamed","year":"2020","journal-title":"Saudi Med. J."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"273","DOI":"10.5144\/0256-4947.2013.273","article-title":"Risk factors for congenital hypothyroidism in Egypt: Results of a population case-control study (2003\u20132010)","volume":"33","author":"Abdelmoktader","year":"2013","journal-title":"Ann. Saudi Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.2147\/NDT.S176198","article-title":"Clinical and neuropsychological outcomes for children with phenylketonuria in Upper Egypt; a single-center study over 5 years","volume":"14","author":"Sadek","year":"2018","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/cge.12786","article-title":"National G6PD neonatal screening program in Gaza Strip of Palestine: Rationale, challenges and recommendations","volume":"90","author":"Sirdah","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_113","first-page":"482","article-title":"D\u00e9pistage Syst\u00e9matique de la Surdit\u00e9 en Maternit\u00e9 par Oto-Emissions Acoustiques Provoqu\u00e9es (OTEAP): Etude Pilote","volume":"88","author":"Nouaili","year":"2010","journal-title":"Tunis. M\u00e9d."},{"key":"ref_114","first-page":"49","article-title":"Cousin marriage and premarital carrier matching in a Bedouin community in Israel: Attitudes, service development and educational intervention","volume":"30","author":"Raz","year":"2004","journal-title":"BMJ. Sex. Reprod. Health"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/0277-9536(94)00433-T","article-title":"Pre-marital genetic counselling to consanguineous couples: Attitudes, beliefs and decisions among counselled, noncounselled and unrelated couples in Israel","volume":"41","author":"Shiloh","year":"1995","journal-title":"Soc. Sci. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000083340","article-title":"Campaign to control genetic blood diseases in Bahrain","volume":"8","year":"2005","journal-title":"Public Health Genom."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"284","DOI":"10.4103\/0256-4947.65256","article-title":"Public awareness of sickle cell disease in Bahrain","volume":"30","year":"2010","journal-title":"Ann. Saudi Med."},{"key":"ref_118","unstructured":"Zitouna, N., Zekri, L.A., Wardi, N., Marrakchi, J., Bouattour, Y., and Ben Hassine, H. (2019, January 16\u201317). Setting-up of a Science Shop project on the early detection of hearing impairment among preschool and school children. Proceedings of the Inaugural Meeting of the Hearing Institute, Coll\u00e8ge de France, Paris, France."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:32:41Z","timestamp":1760167961000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/11\/1820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,19]]},"references-count":118,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["genes12111820"],"URL":"https:\/\/doi.org\/10.3390\/genes12111820","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,19]]}}}