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Postnatal microcephaly and pain insensitivity due to a de novo heterozygous DNM1L mutation causing impaired mitochondrial fission and function.
- Source :
- American Journal of Medical Genetics. Part A; Jun2016, Vol. 170A Issue 6, p1603-1607, 5p
- Publication Year :
- 2016
-
Abstract
- 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. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524825
- Volume :
- 170A
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- American Journal of Medical Genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 115400753
- Full Text :
- https://doi.org/10.1002/ajmg.a.37624