Molecular and clinical studies in SCA-7 define a broad clinical spectrum and the infantile phenotype.
OBJECTIVE
To screen for the SCA-7 mutation in autosomal dominant cerebellar ataxia (ADCA) families and study genotype/phenotype correlations.


BACKGROUND
The association of cerebellar ataxia and progressive pigmentary macular dystrophy clinically defines a distinct form of ADCA classified as SCA-7. SCA-7 is caused by expansion of a highly unstable CAG repeat that lies in the coding region of a novel gene on chromosome 3p12-13.


METHODS
We screened 51 ADCA kindreds, in which SCA-1, SCA-2, SCA-3, and SCA6 mutations had been excluded, for the SCA-7 mutation using primers that specifically amplify the SCA-7 CAG repeat.


RESULTS
The SCA-7 mutation was identified in 10 independent families. Normal alleles ranged from 7 to 16 repeats; expanded alleles ranged from 41 to 306 repeats. One allele with 36 repeats was found in an asymptomatic individual carrying an at-risk haplotype. SCA-7 presents a wide spectrum of clinical features including visual loss, dementia, hypoacusia, severe hypotonia, and auditory hallucinations. Juvenile SCA-7 occurs on maternal and paternal transmission of the mutation, whereas the infantile form occurs only on paternal transmission. An infant of African American descent carried the largest SCA-7 expansion (306 CAG repeats) and had severe hypotonia, congestive heart failure, patent ductus arteriosus, cerebral and cerebellar atrophy, and visual loss.


CONCLUSIONS
These data show a wide spectrum of phenotypic abnormalities in SCA-7 and define an infantile phenotype caused by the largest CAG repeat expansion described to date.
Benton
C S
CS
Department of Molecular and Human Genetics, Baylor College of Medicine and Howard Hughes Medical Institute, Houston, TX 77030, USA.
de Silva
R
R
Rutledge
S L
SL
Bohlega
S
S
Ashizawa
T
T
Zoghbi
H Y
HY
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D000067719:Ataxin-7; D004252:DNA Mutational Analysis; D005192:Family Health; D005838:Genotype; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics*; D018911:Trinucleotide Repeats
C000593829:ATXN7 protein, human; D000067719:Ataxin-7; D009419:Nerve Tissue Proteins