The repeat variant in MSH3 is not a genetic modifier for spinocerebellar ataxia type 3 and Friedreich's ataxia.
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ABSTRACT:
SUBMITTER: Yau WY
PROVIDER: S-EPMC7174052 | biostudies-literature | 2020 Apr
REPOSITORIES: biostudies-literature
Publications
The repeat variant in MSH3 is not a genetic modifier for spinocerebellar ataxia type 3 and Friedreich's ataxia.
Yau Wai Yan WY Raposo Mafalda M Bettencourt Conceição C Labrum Robyn R Vasconcelos João J Parkinson Michael H MH Giunti Paola P Wood Nicholas W NW Lima Manuela M Houlden Henry H
Brain : a journal of neurology 20200401 4
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Project description:Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by ataxia, seizures, and anticipation. It is caused by an expanded ATTCT pentanucleotide repeat in intron 9 of a novel gene, designated "SCA10." The ATTCT expansion in SCA10 represents a novel class of microsatellite repeat and is one of the largest found to cause human diseases. The expanded ATTCT repeat is unstably transmitted from generation to generation, and an inverse correlation has been observed between size of repeat and age at onset. In this multifamily study, we investigated the intergenerational instability, somatic and germline mosaicism, and age-dependent repeat-size changes of the expanded ATTCT repeat. Our results showed that (1) the expanded ATTCT repeats are highly unstable when paternally transmitted, whereas maternal transmission resulted in significantly smaller changes in repeat size; (2) blood leukocytes, lymphoblastoid cells, buccal cells, and sperm have a variable degree of mosaicism in ATTCT expansion; (3) the length of the expanded repeat was not observed to change in individuals over a 5-year period; and (4) clinically determined anticipation is sometimes associated with intergenerational contraction rather than expansion of the ATTCT repeat.
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