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- Title
Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.
- Authors
Kullar, Peter J.; Gomez-Duran, Aurora; Gammage, Payam A.; Garone, Caterina; Minczuk, Michal; Golder, Zoe; Wilson, Janet; Montoya, Julio; Häkli, Sanna; Kärppä, Mikko; Horvath, Rita; Majamaa, Kari; Chinnery, Patrick F.
- Abstract
The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease.
- Subjects
MITOCHONDRIAL DNA; MYOBLASTS; DNA metabolism; EXOMES; SKELETAL muscle; HEARING disorders; DNA; GENES; GENETIC disorders; MITOCHONDRIA; GENETIC mutation; RESEARCH funding; PHENOTYPES; DNA-binding proteins; GENETIC carriers; GENETICS
- Publication
Brain: A Journal of Neurology, 2018, Vol 141, Issue 1, p55
- ISSN
0006-8950
- Publication type
journal article
- DOI
10.1093/brain/awx295