Journal
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
Volume 170, Issue 6, Pages 1603-1607Publisher
WILEY-BLACKWELL
DOI: 10.1002/ajmg.a.37624
Keywords
mitochondrial fission; mitochondrial respiratory chain; mitochondrial dynamics; mitochondrial disease; dynamin-related protein 1; DRP1; DNM1L gene; postnatal microcephaly; pain insensitivity
Categories
Funding
- E-Rare grant GenoMit
- Manackerman Charitable Trust
- Hadassah Compensatory Fund
- Karl Kahane Foundation
Ask authors/readers for more resources
An emerging class of mitochondrial disorders is caused by mutations in nuclear genes affecting mitochondrial dynamics and function. One of these is the DNM1L gene encoding the dynamin-related protein 1 (DRP1), which is pivotal in the mitochondrial fission process. Here, we describe a patient with a novel dominant-negative, de novo DNM1L mutation, which expands the clinical spectrum. The patient reported here exhibits a chronic neurological disorder, characterized by postnatal microcephaly, developmental delay, and pain insensitivity. Muscle biopsy disclosed decreased respiratory chain complex IV activity. Exome sequencing showed a de novo heterozygous c.1084G>A (p.G362S) mutation. Subsequent studies of patient skin fibroblasts showed markedly impaired mitochondrial fission and a partial respiratory chain defect while peroxisomal morphology remained intact. Human foreskin fibroblasts over-expressing the mutant DNM1L gene displayed aberrant mitochondrial morphology. (C) 2016 Wiley Periodicals, Inc.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available