{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:18:49Z","timestamp":1747149529486,"version":"3.40.5"},"reference-count":38,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>MEGDEL syndrome is a rare recessive disorder, with about 100 cases reported worldwide, which is defined by 3\u2010methylglutaconic aciduria (MEG), deafness (D), encephalopathy (E) and Leigh\u2010like syndrome (L). When these manifestations were added to hepatopathy (H), the syndrome was labelled as MEGD(H)EL. Mutations in<jats:italic>SERAC1<\/jats:italic>gene encoding a serine active site containing 1 protein were described in patients affected by this syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and methods<\/jats:title><jats:p>The present study reports the Whole Exome Sequencing (WES) of the first case of MEGDEHL syndrome in Tunisia in a consanguineous family with three affected children. Bioinformatic analysis was also performed in addition to mtDNA deletion screening and mtDNA copy number quantification in the blood of the indexed case, carried out, respectively by Long\u2010Range PCR and qPCR.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The WES revealed a novel homozygous nonsense mutation (c.1379G\u2009&gt;\u2009A; p.W460X) in the<jats:italic>SERAC1<\/jats:italic>gene, which was confirmed by Sanger sequencing. This nonsense mutation was present at a homozygous state in the three affected children and was heterozygous in the parents. In silico analysis using various softwares was performed, and the predictive results supported the pathogenic effect of the identified mutation. Further, long\u2010range PCR and qPCR analyses of the patient's blood excluded any mtDNA deletions or depletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Sequencing results and bioinformatic tools confirmed that the novel mutation (p.W460X) in the<jats:italic>SERAC1<\/jats:italic>gene causes the severe phenotype in the studied family with MEGDEHL syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jdn.10223","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T16:36:21Z","timestamp":1660062981000},"page":"735-746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["First description of the MEGDEHL syndrome in the Tunisian population via whole\u2010exome sequencing: Novel nonsense mutation in<i>SERAC1<\/i>gene"],"prefix":"10.1002","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1497-7237","authenticated-orcid":false,"given":"Rahma","family":"Felhi","sequence":"first","affiliation":[{"name":"Molecular and Functional Genetics Laboratory, Faculty of Science of Sfax University of Sfax Sfax Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Monastiri","sequence":"additional","affiliation":[{"name":"Maternity and Neonatology Center of Monastir Faculty of Medicine of Monastir Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayet","family":"Ben Hamida","sequence":"additional","affiliation":[{"name":"Maternity and Neonatology Center of Monastir Faculty of Medicine of Monastir Monastir Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Ammar","sequence":"additional","affiliation":[{"name":"Molecular and Functional Genetics Laboratory, Faculty of Science 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