Identification of a novel splice site mutation in the SERAC1 gene responsible for the MEGDHEL syndrome.
Mol Genet Genomic Med
; 7(8): e815, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31251474
ABSTRACT
BACKGROUND:
MEGDHEL is an autosomal recessive syndrome defined as 3-MEthylGlutaconic aciduria (3-MGA) with Deafness, Hepatopathy, Encephalopathy, and Leigh-like syndrome on magnetic resonance imaging, due to mutations in the SERAC1 (Serine Active Site Containing 1) gene, which plays a role in the mitochondrial cardiolipin metabolism.METHODS:
We report the case of a young patient who presented with a convulsive encephalopathy, 3-methylglutaconic aciduria, deafness, and bilateral T2 hypersignals of the putamen and the thalami, who passed away at 8 years of age.RESULTS:
Analysis of nuclear genes using an ampliSeq™ targeted custom panel disclosed two compound heterozygous variants in the SERAC1 gene a nonsense substitution in exon 4, c.202C>T, resulting in a premature stop codon (p.Arg68*), and a novel variant at a canonical splicing site upstream exon 4 (c.129-1G>C). mRNAs sequencing from the fibroblasts of the patient showed that the splice site variant resulted in exon 3 skipping without frameshift while Western blot experiments showed the absence of SERAC1 expression compared to controls and abnormal filipin staining.CONCLUSION:
We showed that the loss of the putative transmembrane domain of SERAC1, due to a novel splice site variant, impairs the protein expression and is responsible for the MEGDHEL syndrome.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Encefalopatias
/
Hidrolases de Éster Carboxílico
/
Surdez
/
Erros Inatos do Metabolismo
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article