Somatic and germline instability of the ATTCT repeat in spinocerebellar ataxia type 10.
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.
Matsuura
Tohru
T
Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Fang
Ping
P
Lin
Xi
X
Khajavi
Mehrdad
M
Tsuji
Kuniko
K
Rasmussen
Astrid
A
Grewal
Raji P
RP
Achari
Madhureeta
M
Alonso
Maria E
ME
Pulst
Stefan M
SM
Zoghbi
Huda Y
HY
Nelson
David L
DL
Roa
Benjamin B
BB
Ashizawa
Tetsuo
T
D017677:Age Distribution; D002460:Cell Line; D004247:DNA / Q000097:blood / Q000737:chemistry / Q000235:genetics*; D018562:Disease Transmission, Infectious; D005260:Female; D005799:Genes, Dominant; D005854:Germ Cells; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism / Q000473:pathology; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology
D004247:DNA