Premium
The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome
Author(s) -
Martín M.Á.,
GarcíaSilva M.T.,
Barcia G.,
Delmiro A.,
RodríguezGarcía M.E.,
Blázquez A.,
FranciscoÁlvarez R.,
MartínHernández E.,
QuijadaFraile P.,
TejadaPalacios P.,
Arenas J.,
Santos C.,
MartínezAzorín F.
Publication year - 2017
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12815
Subject(s) - genetics , exome sequencing , mutation , biology , lactic acidosis , gene , mitochondrial dna , exon , disease gene identification , endocrinology
We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole‐exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.