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Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3‐Methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and leigh‐Like Syndrome) caused by novel mutations in SERAC1
Author(s) -
Sarig Ofer,
Goldsher Dorit,
Nousbeck Janna,
FuchsTelem Dana,
CohenKatsenelson Ksenya,
Iancu Theodore C.,
Manov Irena,
Saada Ann,
Sprecher Eli,
Mandel Hanna
Publication year - 2013
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36059
Subject(s) - leigh disease , encephalopathy , sensorineural hearing loss , medicine , mitochondrial dna , pathology , mitochondrial disease , exome sequencing , genetics , mutation , biology , hearing loss , gene , audiology
Abstract 3‐Methylglutaconic aciduria (3‐MGCA) type IV is defined as a heterogeneous group of inborn errors featuring in common 3‐MGCA and associated with primary mitochondrial dysfunction leading to a spectrum of multisystem conditions. We studied four patients who presented at birth with a clinical picture simulating a primary mitochondrial hepatic disorder consistent with the MEGDEL syndrome including 3‐MGCA, sensorineural deafness, encephalopathy and a brain magnetic resonance imaging with signs of Leigh disease. All affected children displayed biochemical features consistent with mitochondrial OXPHOS dysfunction including hepatic mitochondrial DNA depletion in one patient. Homozygosity mapping identified a candidate locus on 6q25.2‐6q26. Using whole exome sequencing, we identified two novel homozygous mutations in SERAC1 recently reported to harbor mutations in MEGDEL syndrome. Both mutations were found to lead to decreased or absent expression of SERAC1 . The present findings indicate that infantile hepatopathy is a cardinal feature of MEGDEL syndrome. We thus propose to rename the disease MEGDHEL syndrome. © 2013 Wiley Periodicals, Inc.