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.
Department of Molecular and Human Genetics, Baylor College of Medicine and Howard Hughes Medical Institute, Houston, TX 77030, USA.
C S
CS
Benton
R
R
de Silva
S L
SL
Rutledge
S
S
Bohlega
T
T
Ashizawa
H Y
HY
Zoghbi
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