Files and links (1)
Accepted (AM)Open Access (License Unspecified), Open
Journal article
Mutation in the Novel Nuclear-Encoded Mitochondrial Protein CHCHD10 in a Family with Autosomal Dominant Mitochondrial Myopathy
Neurogenetics, v 16(1), pp 1-9
06 Sep 2014
PMID: 25193783
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Mitochondrial myopathies belong to a larger group of systemic diseases caused by morphological or biochemical abnormalities of mitochondria. Mitochondrial disorders can be caused by mutations in either the mitochondrial or the nuclear genome. Only 5% of all mitochondrial disorders are autosomal dominant. We analyzed DNA from members of a previously reported Puerto Rican kindred with an autosomal dominant mitochondrial myopathy (Heimann-Patterson et al. 1997). Linkage analysis suggested a putative locus on the pericentric region of the long arm of chromosome 22 (22q11). Using the tools of integrative genomics, we established
C22orf16
(later designated as
CHCHD10
) as the only high scoring mitochondrial candidate gene in our minimal candidate region. Sequence analysis revealed a double missense mutation (R15S; G58R) in
cis
in
CHCHD10
which encodes a coiled-coil helix coiled-coil helix protein of unknown function. These two mutations completely co-segregated with the disease phenotype and were absent in 1481 Caucasian and 80 Hispanic (including 32 Puerto Rican) controls. Expression profiling showed that
CHCHD10
is enriched in skeletal muscle. Mitochondrial localization of the CHCHD10 protein was confirmed using immunofluorescence in cells expressing either wild-type or mutant CHCHD10. We found that expression of the G58R, but not the R15S, mutation induced mitochondrial fragmentation. Our findings identify a novel gene causing mitochondrial myopathy, thereby expanding the spectrum of mitochondrial myopathies caused by nuclear genes. Our findings also suggest a role for CHCHD10 in the morphologic remodeling of the mitochondria.
Metrics
Details
- Title
- Mutation in the Novel Nuclear-Encoded Mitochondrial Protein CHCHD10 in a Family with Autosomal Dominant Mitochondrial Myopathy
- Creators
- Senda Ajroud-Driss - Northwestern UniversityFaisal Fecto - Northwestern UniversityKaouther Ajroud - Northwestern UniversityIrfan Lalani - Northwestern UniversitySarah E. Calvo - Howard Hughes Medical InstituteVamsi K. Mootha - Howard Hughes Medical InstituteHan-Xiang Deng - Division of Neuromuscular Medicine, The Ken and Ruth Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Interdepartmental Neuroscience Program, Northwestern University, Chicago, IL, USA Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA Department of Systems Biology, Harvard Medical School, Boston, MA, USA Broad Institute, Cambridge, MA, USA Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USANailah Siddique - Northwestern UniversityAlbert J. Tahmoush - Thomas Jefferson UniversityTerry D. Heiman-Patterson - Drexel UniversityTeepu Siddique - Northwestern University
- Publication Details
- Neurogenetics, v 16(1), pp 1-9
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000347408700001
- Scopus ID
- 2-s2.0-84920528572
- Other Identifier
- 991019173813604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Genetics & Heredity