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

Orphanet J Rare Dis 2016 10 21;11(1):139. Epub 2016 Oct 21.

Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al-Ain, United Arab Emirates.

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.

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http://dx.doi.org/10.1186/s13023-016-0526-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5073853PMC
October 2016
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References

(Supplied by CrossRef)

T Suzuki et al.
Wiley Interdiscip Rev RNA 2011

O Russell et al.
Exp Cell Res 2014

TB Haack et al.
Am J Hum Genet 2013

LK Brzezniak et al.
RNA Biol 2011

NA Akawi et al.
Orphanet J Rare Dis 2013

NA Akawi et al.
Am J Med Genet A 2016

W Rossmanith et al.
Biochim Biophys Acta 2012

MI Sanchez et al.
Cell Cycle 2011

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