Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood.

ABSTRACT:

Objective

To define the mechanism responsible for fatigue, lethargy, and weakness in 2 cousins who had a normal muscle biopsy.

Methods

Exome sequencing, long-range PCR, and Sanger sequencing to identify the pathogenic mutation. Functional analysis in the patient fibroblasts included oxygen consumption measurements, extracellular acidification studies, Western blotting, and calcium imaging, followed by overexpression of the wild-type protein.

Results

Analysis of the exome sequencing depth revealed a homozygous deletion of exon 1 of MICU1 within a 2,755-base pair deletion. No MICU1 protein was detected in patient fibroblasts, which had impaired mitochondrial calcium uptake that was rescued through the overexpression of the wild-type allele.

Conclusions

MICU1 muta

SUBMITTER: Lewis-Smith D 

PROVIDER: S-EPMC4830195 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature