Post-zygotic de novo trinucleotide repeat expansion at spinocerebellar ataxia type 7 locus: evidence from an Indian family.
Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansion. We found expansion at SCA7 locus in only two out of 235 Indian families clinically diagnosed for ataxia. In one of the families, a de novo mutation was observed wherein a paternal allele in intermediate range of 31 CAG repeats expanded to 59 in the offspring leading to the disease. No expanded alleles were observed in the sperm of the transmitting parent by small pool PCR. This suggests that de novo expansion by a pre-zygotic event is unlikely and could be post-zygotic. SCA7 expanded alleles from the two families were present on different genetic backgrounds, indicating multiple origins of the mutation.
Mittal
Uma
U
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110007, India.
Roy
Sanghamitra
S
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110007, India.
Jain
Satish
S
Neuroscience Centre, All India Institute of Medical Sciences, New Delhi, India.|Indian Epilepsy Centre, Defence Colony, New Delhi, India.
Srivastava
Achal K
AK
Neuroscience Centre, All India Institute of Medical Sciences, New Delhi, India.
Mukerji
Mitali
M
Functional Genomics Unit, Institute of Genomics and Integrative Biology, CSIR, Mall Road, Delhi, 110007, India. mitali@igib.res.in.
D042622:DNA Repeat Expansion / Q000235:genetics*; D006801:Humans; D007194:India; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D017422:Sequence Analysis, DNA; D020754:Spinocerebellar Ataxias / Q000235:genetics*