A homozygous splicing mutation in ELAC2 suggests phenotypic variability including intellectual disability with minimal cardiac involvement

Nadia A. Akawi, Salma Ben-Salem, Jozef Hertecant, Anne John, Thachillath Pramathan, Praseetha Kizhakkedath, Bassam R. Ali, Lihadh Al-Gazali

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Article number139
JournalOrphanet Journal of Rare Diseases
Volume11
Issue number1
DOIs
Publication statusPublished - Oct 21 2016

Keywords

  • 5′ end unprocessed mt-RNAs
  • ELAC2
  • Intellectual disability
  • Mitochondrial disorder
  • Respiratory chain complex I (RCCI) deficiency
  • Splice site mutation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Pharmacology (medical)

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