Identification of a novel splice site mutation in the SERAC1 gene responsible for the MEGDHEL syndrome.
Brain
/ diagnostic imaging
Brain Diseases
/ diagnosis
Carboxylic Ester Hydrolases
/ genetics
Child
Deafness
/ diagnosis
Exons
/ genetics
Fatal Outcome
Humans
Magnetic Resonance Imaging
Male
Metabolism, Inborn Errors
/ diagnosis
Pedigree
Protein Domains
/ genetics
RNA Splice Sites
/ genetics
Syndrome
SERAC1
3-MGA
MEGDHEL
cardiolipin metabolism
mitochondria
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
09
01
2019
revised:
12
02
2019
accepted:
16
05
2019
pubmed:
30
6
2019
medline:
1
7
2020
entrez:
29
6
2019
Statut:
ppublish
Résumé
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. 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. Analysis of nuclear genes using an ampliSeq 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.
Sections du résumé
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
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.
Identifiants
pubmed: 31251474
doi: 10.1002/mgg3.815
pmc: PMC6687635
doi:
Substances chimiques
RNA Splice Sites
0
Carboxylic Ester Hydrolases
EC 3.1.1.-
SERAC1 protein, human
EC 3.1.1.-
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e815Informations de copyright
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.
Références
Ann Neurol. 2017 Dec;82(6):1004-1015
pubmed: 29205472
Nat Genet. 2012 Jun 10;44(7):797-802
pubmed: 22683713
Neurogenetics. 2016 Jan;17(1):51-6
pubmed: 26445863
Nucleic Acids Res. 2009 May;37(9):e67
pubmed: 19339519
Neuropediatrics. 2015 Apr;46(2):98-103
pubmed: 25642805
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W337-43
pubmed: 24799431
Bioinformatics. 2007 May 15;23(10):1289-91
pubmed: 17379693
Front Genet. 2015 Feb 03;6:3
pubmed: 25691889
Am J Med Genet A. 2013 Sep;161A(9):2204-15
pubmed: 23918762
J Med Genet. 2018 Jan;55(1):39-47
pubmed: 28916646
J Comput Biol. 2004;11(2-3):377-94
pubmed: 15285897
Mol Genet Genomic Med. 2019 Aug;7(8):e815
pubmed: 31251474
Mol Genet Metab. 2013 Sep-Oct;110(1-2):73-7
pubmed: 23707711
Nucleic Acids Res. 2012 Aug;40(15):e115
pubmed: 22730293
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
JIMD Rep. 2014;16:1-6
pubmed: 24757000
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):4158-4163
pubmed: 29618609
Mitochondrion. 2009 Sep;9(5):331-9
pubmed: 19439198
Biochimie. 2017 Nov;142:102-111
pubmed: 28842204