{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:47:08Z","timestamp":1783579628147,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["2015\/19\/B\/NZ2\/01824"],"award-info":[{"award-number":["2015\/19\/B\/NZ2\/01824"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Congenital microcephaly causes smaller than average head circumference relative to age, sex and ethnicity and is most usually associated with a variety of neurodevelopmental disorders. The underlying etiology is highly heterogeneous and can be either environmental or genetic. Disruption of any one of multiple biological processes, such as those underlying neurogenesis, cell cycle and division, DNA repair or transcription regulation, can result in microcephaly. This etiological heterogeneity manifests in a clinical variability and presents a major diagnostic and therapeutic challenge, leaving an unacceptably large proportion of over half of microcephaly patients without molecular diagnosis. To elucidate the clinical and genetic landscapes of congenital microcephaly, we sequenced the exomes of 191 clinically diagnosed patients with microcephaly as one of the features. We established a molecular basis for microcephaly in 71 patients (37%), and detected novel variants in five high confidence candidate genes previously unassociated with this condition. We report a large number of patients with mutations in tubulin-related genes in our cohort as well as higher incidence of pathogenic mutations in MCPH genes. Our study expands the phenotypic and genetic landscape of microcephaly, facilitating differential clinical diagnoses for disorders associated with most commonly disrupted genes in our cohort.<\/jats:p>","DOI":"10.3390\/genes12122014","type":"journal-article","created":{"date-parts":[[2021,12,19]],"date-time":"2021-12-19T20:37:27Z","timestamp":1639946247000},"page":"2014","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exome Sequencing Reveals Novel Variants and Expands the Genetic Landscape for Congenital Microcephaly"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-8722","authenticated-orcid":false,"given":"Mateusz","family":"Dawidziuk","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-1696","authenticated-orcid":false,"given":"Ewelina","family":"Bukowska-Olech","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Antczak-Marach","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Badura-Stronka","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Buda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nutrition, and Metabolic Diseases, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edyta","family":"Budzynska","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Central Clinical Hospital, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Castaneda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Chilarska","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital Research Institute, 93-338 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Czyzyk","sequence":"additional","affiliation":[{"name":"Clinical Department of Child Neurology, Clinical Central Hospital No. 2 in Rzeszow, 35-301 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Eckersdorf-Mastalerz","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Central Clinical Hospital, Medical University of Lodz, 92-213 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolanta","family":"Fijak-Moskal","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Gieruszczak-Bialek","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Medical University of Warsaw, 01-184 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Glodek-Brzozowska","sequence":"additional","affiliation":[{"name":"Clinical Department of Child Neurology, Clinical Central Hospital No. 2 in Rzeszow, 35-301 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicja","family":"Goszczanska-Ciuchta","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Grzeszykowska-Podymniak","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Kidney Transplantation and Hypertension, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Gurda","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurology, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jakubiuk-Tomaszuk","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology and Rehabilitation, Medical University of Bialystok, 15-274 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Jamroz","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Neurology of Developmental Age, Saint John Paul II Upper Silesian Child Health Centre, The Independent Public Clinical Hospital No. 6 of the Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Janeczko","sequence":"additional","affiliation":[{"name":"Department of Genetics, Institute of Pediatrics, Jagiellonian University Medical College, 30-663 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Jedli\u0144ska-Pijanowska","sequence":"additional","affiliation":[{"name":"Department of Neonatology and Neonatal Intensive Care, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Jurek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmara","family":"Karolewska","sequence":"additional","affiliation":[{"name":"Specialist Mother and Child Hospital Complex in Poznan, 61-825 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adela","family":"Kazmierczak","sequence":"additional","affiliation":[{"name":"Independent Public Healthcare Center, Department of Pediatric Neurology, Multidisciplinary Hospital, 67-100 Nowa Sol, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Kleist","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Neurological Outpatient Clinic for Children, Municipal Hospital Complex, 41-500 Chorzow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Kochanowska","sequence":"additional","affiliation":[{"name":"Individual Medical Practice in Pediatric Neurology, 70-592 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-210X","authenticated-orcid":false,"given":"Malgorzata","family":"Krajewska-Walasek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"},{"name":"Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Kufel","sequence":"additional","affiliation":[{"name":"Department of Neonatal and Intensive Care, Medical University of Warsaw, 01-184 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5295-7363","authenticated-orcid":false,"given":"Anna","family":"Kutkowska-Ka\u017amierczak","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Lipiec","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Maksym-Gasiorek","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Neonatal Pathology and Intensive Care, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2889-5892","authenticated-orcid":false,"given":"Anna","family":"Materna-Kiryluk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Polish Registry of Congenital Malformations, Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mazurkiewicz","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Milewski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsiana","family":"Pavina-Guglas","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Neonatal Pathology and Intensive Care, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Pietrzyk","sequence":"additional","affiliation":[{"name":"Department of Genetics and Pathomorphology, Faculty of Medicine and Health Sciences, University of Zielona Gora, 65-046 Zielona Gora, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Posmyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Pyrkosz","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Rzeszow, 35-959 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Rudzka-Dybala","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6738-9565","authenticated-orcid":false,"given":"Ryszard","family":"Slezak","sequence":"additional","affiliation":[{"name":"Department of Genetics, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"Wisniewska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zofia","family":"Zalewska-Miszkurka","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Szczepanik","sequence":"additional","affiliation":[{"name":"Clinic of Paediatric Neurology, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1787-3425","authenticated-orcid":false,"given":"Monika","family":"Bekiesinska-Figatowska","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Imaging, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3672-5834","authenticated-orcid":false,"given":"Pawel","family":"Gawlinski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Wiszniewski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of Mother and Child, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.conb.2004.01.003","article-title":"Human microcephaly","volume":"14","author":"Woods","year":"2004","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1111\/dmcn.12425","article-title":"Diagnostic approach to microcephaly in childhood: A two-center study and review of the literature","volume":"56","author":"Pivarcsi","year":"2014","journal-title":"Dev. Med. Child Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1136\/archdischild-2012-302882","article-title":"Investigating microcephaly","volume":"98","author":"Woods","year":"2013","journal-title":"Arch. Dis. Child."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Faheem, M., Naseer, M.I., Rasool, M., Chaudhary, A.G., Kumosani, T.A., Ilyas, A.M., Pushparaj, P.N., Ahmed, F., Algahtani, H.A., and Al-Qahtani, M.H. (2015). Molecular genetics of human primary microcephaly: An overview. BMC Med. Genom., 8.","DOI":"10.1186\/1755-8794-8-S1-S4"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/ajmg.c.31400","article-title":"Genetic disorders associated with postnatal microcephaly","volume":"166","author":"Seltzer","year":"2014","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/ajmg.c.31397","article-title":"Congenital microcephaly","volume":"166","author":"Alcantara","year":"2014","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1001\/jama.2014.14601","article-title":"Molecular Findings Among Patients Referred for Clinical Whole-Exome Sequencing","volume":"312","author":"Yang","year":"2014","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"547986","DOI":"10.1155\/2014\/547986","article-title":"Molecular and Cellular Basis of Autosomal Recessive Primary Microcephaly","volume":"2014","author":"Barbelanne","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1093\/brain\/awz004","article-title":"Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish","volume":"142","author":"Perez","year":"2019","journal-title":"Brain"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rump, P., Jazayeri, O., van Dijk-Bos, K.K., Johansson, L.F., van Essen, A.J., Verheij, J.B.G.M., Veenstra-Knol, H.E., Redeker, E.J.W., Mannens, M.M.A.M., and Swertz, M.A. (2015). Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. BMC Med. Genom., 9.","DOI":"10.1186\/s12920-016-0167-8"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1038\/s41436-019-0464-7","article-title":"Elucidation of the phenotypic spectrum and genetic landscape in primary and secondary microcephaly","volume":"21","author":"Boonsawat","year":"2019","journal-title":"Genet. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41436-018-0140-3","article-title":"Genomic and phenotypic delineation of congenital microcephaly","volume":"21","author":"Shaheen","year":"2018","journal-title":"Genet. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and Accurate Short Read Alignment with Burrows-Wheeler Transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Poplin, R., Ruano-Rubio, V., DePristo, M.A., Fennell, T.J., Carneiro, M.O., van der Auwera, G.A., Kling, D.E., Gauthier, L.D., Levy-Moonshine, A., and Roazen, D. (2017). Scaling accurate genetic variant discovery to tens of thousands of samples. BioRxiv, 201178.","DOI":"10.1101\/201178"},{"key":"ref_15","unstructured":"Chapman, B., Kirchner, R., Pantano, L., Khotiainsteva, T., Smet, M.D., Beltrame, L., Saveliev, V., Guimera, R.V., Nau-menko, S., and Kern, J. (2019). Bcbio\/Bcbio-Nextgen: V1.1.9, Zenodo."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","article-title":"The Ensembl Variant Effect Predictor","volume":"17","author":"McLaren","year":"2016","journal-title":"Genome Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","article-title":"ClinVar: Public archive of interpretations of clinically relevant variants","volume":"44","author":"Landrum","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s13073-020-00803-9","article-title":"dbNSFP v4: A comprehensive database of transcript-specific functional predictions and annotations for human nonsynonymous and splice-site SNVs","volume":"12","author":"Liu","year":"2020","journal-title":"Genome Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1101\/gr.138115.112","article-title":"Copy number variation detection and genotyping from exome sequence data","volume":"22","author":"Krumm","year":"2012","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1093\/bioinformatics\/btx699","article-title":"Mosdepth: Quick Coverage Calculation for Genomes and Exomes","volume":"34","author":"Pedersen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1093\/bioinformatics\/bts503","article-title":"Qualimap: Evaluating next-generation sequencing alignment data","volume":"28","author":"Okonechnikov","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1093\/brain\/awu082","article-title":"The wide spectrum of tubulinopathies: What are the key features for the diagnosis?","volume":"137","author":"Poirier","year":"2014","journal-title":"Brain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41431-017-0038-6","article-title":"HUWE1 variants cause dominant X-linked intellectual disability: A clinical study of 21 patients","volume":"26","author":"Moortgat","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1136\/jmg.2009.076398","article-title":"A clinical and molecular genetic study of 112 Iranian families with primary microcephaly","volume":"47","author":"Darvish","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1111\/epi.16319","article-title":"Phenotypic and genetic spectrum of SCN 8A -related disorders, treatment options, and outcomes","volume":"60","author":"Gardella","year":"2019","journal-title":"Epilepsia"},{"key":"ref_30","first-page":"1013","article-title":"Mutation update for the SATB2 gene","volume":"40","author":"Zarate","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1111\/epi.16480","article-title":"KCNT1-related epilepsy: An international multicenter cohort of 27 pediatric cases","volume":"61","author":"Borlot","year":"2020","journal-title":"Epilepsia"},{"key":"ref_32","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Mirzaa, G., and Amemiya, A. (1993). GRIN1-Related Neurodevelopmental Disorder. GeneReviews\u00ae, University of Washington."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"850","DOI":"10.3389\/fped.2020.575673","article-title":"Case Report: A de novo CTNNB1 Nonsense Mutation Associated with Neurodevelopmental Disorder, Retinal Detachment, Polydactyly","volume":"8","author":"Ke","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1542","DOI":"10.1002\/mgg3.1542","article-title":"Missense variants in CTNNB1 can be associated with vitreoretinopathy\u2014Seven new cases of CTNNB1 -associated neurodevelopmental disorder including a previously unreported retinal phenotype","volume":"9","author":"Rossetti","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_35","first-page":"487","article-title":"A de novo CTNNB1 novel splice variant in an adult female with severe intellectual disability","volume":"13","author":"Verhoeven","year":"2020","journal-title":"Int. Med. Case Rep. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/gim.2017.75","article-title":"FOXG1 syndrome: Genotype\u2013phenotype association in 83 patients with FOXG1 variants","volume":"20","author":"Mitter","year":"2018","journal-title":"Genet. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/humu.22924","article-title":"Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update","volume":"37","author":"Huang","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_38","first-page":"875","article-title":"Syndrome of the Month Pyruvate Dehydrogenase Deficiency","volume":"31","author":"Brown","year":"1994","journal-title":"Amino Acids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s13023-020-01586-3","article-title":"Pyruvate dehydrogenase complex deficiency: Updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients","volume":"15","author":"Silva","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_40","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J., Mirzaa, G., and Amemiya, A. (1993). ASPM Primary Microcephaly. GeneReviews\u00ae, University of Washington."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/ajmg.a.37724","article-title":"Molecular and phenotypic spectrum of ASPM-related primary microcephaly: Identification of eight novel mutations","volume":"170","author":"Ismail","year":"2016","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1056\/NEJMoa1516767","article-title":"Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation","volume":"376","author":"Posey","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1212\/WNL.0000000000002740","article-title":"Delineating the GRIN1 phenotypic spectrum","volume":"86","author":"Lemke","year":"2016","journal-title":"Neurology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1136\/jmedgenet-2019-106377","article-title":"Clinical exome sequencing as the first-tier test for diagnosing developmental disorders covering both CNV and SNV: A Chinese cohort","volume":"57","author":"Dong","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1093\/nar\/gkf647","article-title":"Localisation of the human hSuv3p helicase in the mitochondrial matrix and its preferential unwinding of dsDNA","volume":"30","author":"Minczuk","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1042\/BC20060108","article-title":"Down-regulation of human RNA\/DNA helicase SUV3 induces apoptosis by a caspase- and AIF-dependent pathway","volume":"99","author":"Szczesny","year":"2007","journal-title":"Biol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1042\/BJ20060450","article-title":"Mechanisms of RecQ helicases in pathways of DNA metabolism and maintenance of genomic stability","volume":"398","author":"Sharma","year":"2006","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.arr.2016.05.010","article-title":"Bloom\u2019s syndrome: Why not premature aging?","volume":"33","author":"Ellis","year":"2017","journal-title":"Ageing Res. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ejmg.2017.10.010","article-title":"Bloom syndrome does not always present with sun-sensitive facial erythema","volume":"61","author":"Bouman","year":"2018","journal-title":"Eur. J. Med. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"15389","DOI":"10.1073\/pnas.1206131109","article-title":"Conditional control of gene function by an invertible gene trap in zebrafish","volume":"109","author":"Ni","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.mad.2007.09.001","article-title":"Interaction of human SUV3 RNA\/DNA helicase with BLM helicase; loss of the SUV3 gene results in mouse embryonic lethality","volume":"128","author":"Pereira","year":"2007","journal-title":"Mech. Ageing Dev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"22798","DOI":"10.1074\/jbc.M114.568535","article-title":"Suppression of the DHX9 Helicase Induces Premature Senescence in Human Diploid Fibroblasts in a p53-dependent Manner","volume":"289","author":"Lee","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e18825","DOI":"10.7554\/eLife.18825","article-title":"Human Nup98 regulates the localization and activity of DExH\/D-box helicase DHX9","volume":"6","author":"Capitanio","year":"2017","journal-title":"Elife"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nature21715","article-title":"DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome","volume":"544","author":"Aktas","year":"2017","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4346","DOI":"10.1038\/s41467-018-06677-1","article-title":"DHX9 helicase promotes R-loop formation in cells with impaired RNA splicing","volume":"9","author":"Chakraborty","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"42716","DOI":"10.18632\/oncotarget.8446","article-title":"The biology of DHX9 and its potential as a therapeutic target","volume":"7","author":"Lee","year":"2016","journal-title":"Oncotarget"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1083\/jcb.200708004","article-title":"Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP","volume":"181","author":"Kawahara","year":"2008","journal-title":"J. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3621","DOI":"10.1002\/stem.2202","article-title":"A Mouse Model of Targeted Musashi1 Expression in Whole Intestinal Epithelium Suggests Regulatory Roles in Cell Cycle and Stemness","volume":"33","author":"Cambuli","year":"2015","journal-title":"St. Cells"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Murphy, D., Cieply, B., Carstens, R., Ramamurthy, V., and Stoilov, P. (2016). The Musashi 1 Controls the Splicing of Photoreceptor-Specific Exons in the Vertebrate Retina. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1006256"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12125","DOI":"10.1074\/jbc.M809605200","article-title":"Genomic Analyses of Musashi1 Downstream Targets Show a Strong Association with Cancer-related Processes","volume":"284","author":"Abreu","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Siskos, N., Stylianopoulou, E., Skavdis, G., and Grigoriou, M. (2021). Molecular Genetics of Microcephaly Primary Hereditary: An Overview. Brain Sci., 11.","DOI":"10.3390\/brainsci11050581"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.aam9243","article-title":"Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication","volume":"357","author":"Chavali","year":"2017","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1016\/j.cell.2015.10.065","article-title":"A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface","volume":"163","author":"Gupta","year":"2015","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1021\/acs.jproteome.0c00516","article-title":"The Functionally Unannotated Proteome of Human Male Tissues: A Shared Resource to Uncover New Protein Functions Associated with Reproductive Biology","volume":"19","author":"Vandenbrouck","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e07519","DOI":"10.7554\/eLife.07519","article-title":"Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication","volume":"4","author":"Kodani","year":"2015","journal-title":"Elife"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4501","DOI":"10.1038\/ncomms5501","article-title":"Elfn1 recruits presynaptic mGluR7 in trans and its loss results in seizures","volume":"5","author":"Tomioka","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Dolan, J., and Mitchell, K.J. (2013). Mutation of Elfn1 in Mice Causes Seizures and Hyperactivity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080491"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.neuron.2015.09.002","article-title":"Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision","volume":"87","author":"Cao","year":"2015","journal-title":"Neuron"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/2014\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:45Z","timestamp":1760169105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/12\/2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,18]]},"references-count":68,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["genes12122014"],"URL":"https:\/\/doi.org\/10.3390\/genes12122014","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,18]]}}}