A homozygous splicing mutation in ELAC2 suggests phenotypic variability including intellectual disability with minimal cardiac involvement.
Orphanet J Rare Dis
; 11(1): 139, 2016 10 21.
Article
em En
| MEDLINE
| ID: mdl-27769300
ABSTRACT
BACKGROUND:
The group of ELAC2-related encephalomyopathies is a recent addition to the rapidly growing heterogeneous mitochondrial disorders.RESULTS:
We describe a highly inbred consanguineous Pakistani family with multiple affected children in 2 branches exhibiting moderately severe global developmental delay. Using homozygosity mapping, we mapped the phenotype in this family to a single locus on chromosome 17. In addition, whole-exome sequencing identified a homozygous splicing mutation (c.1423 + 2 T > A) in ELAC2 gene that disrupted the canonical donor splice site of intron 15 of all known isoforms. A noticeable reduction in ELAC2 expression was observed in patients compared to controls. In addition, patients exhibited significantly increased levels of 5' end unprocessed mt-RNAs compared to the control fibroblast cells.CONCLUSIONS:
The only three previously reported families with defects in ELAC2 gene exhibited infantile hypertrophic cardiomyopathy and complex I deficiency. In contrast, our patients exhibited intellectual disability as the main feature with minimal cardiac involvement. Therefore our findings expand the phenotypic spectrum of ELAC2- associated disorders illustrating clinical heterogeneity of mutations in this gene. In addition, ELAC2 mutations should be considered when evaluating patient with mainly intellectual disability phenotypes.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Deficiência Intelectual
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article