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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.

Original publication

DOI

10.1186/s13023-016-0526-8

Type

Journal article

Journal

Orphanet J Rare Dis

Publication Date

21/10/2016

Volume

11

Keywords

5′ end unprocessed mt-RNAs, ELAC2, Intellectual disability, Mitochondrial disorder, Respiratory chain complex I (RCCI) deficiency, Splice site mutation, Child, Preschool, DNA, Mitochondrial, Exome, Female, High-Throughput Nucleotide Sequencing, Homozygote, Humans, Infant, Intellectual Disability, Male, Mutation, Neoplasm Proteins, RNA Splice Sites, RNA Splicing