{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,21]],"date-time":"2025-12-21T12:03:57Z","timestamp":1766318637331,"version":"3.40.5"},"reference-count":38,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder due to defects in the branched\u2010chain \u03b1\u2010ketoacid dehydrogenase complex (BCKDC). MSUD varies in severity and its clinical spectrum is quite broad, ranging from mild to severe phenotypes. Thirty\u2010three MSUD patients were recruited into this study for molecular genetic variant profiling and genotype\u2013phenotype correlation. Except for one patient, all other patients presented with the classic neonatal form of the disease. Seventeen different variants were detected where nine were novel. The detected variants spanned across the entire <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic> and <jats:italic>DBT<\/jats:italic> genes. All variants were in homozygous forms. The commonest alterations were nonsense and frameshift variants, followed by missense variants. For the prediction of variant's pathogenicity, we used molecular modeling and several in silico tools including SIFT, Polyphen2, Condel, and Provean. In addition, six other tools were used for the prediction of the conservation of the variants' sites including Eigen\u2010PC, GERP++, SiPhy, PhastCons vertebrates and primates, and PhyloP100 rank scores. Herein, we presented a comprehensive characterization of a large cohort of patients with MSUD. The clinical severity of the variants' phenotypes was well correlated with the genotypes. The study underscores the importance of the use of in silico analysis of MSUD genotypes for the prediction of the clinical outcomes in patients with MSUD.<\/jats:p>","DOI":"10.1002\/ajmg.a.61806","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T03:14:25Z","timestamp":1598584465000},"page":"2486-2500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Genotype\u2013phenotype correlation of 33 patients with maple syrup urine disease"],"prefix":"10.1002","volume":"182","author":[{"given":"Ola A.","family":"Khalifa","sequence":"first","affiliation":[{"name":"Genetics Unit, Department of Pediatrics, Faculty of Medicine Ain Shams University  Cairo Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faiqa","family":"Imtiaz","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Centre  Riyadh Saudi 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