SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2.
We describe a four-generation Italian family with a novel form of juvenile-onset, slowly progressive, autosomal dominant cerebellar ataxia. Eleven affected family members have been evaluated. The mean age at onset was 19.5 years with no evidence of anticipation. The first symptoms were invariably unbalanced standing and mild gait incoordination. Gaze-evoked nystagmus was prominent at onset, while patients with longer disease duration developed slow saccades, ophthalmoparesis and, often, ptosis. Deep tendon reflexes in lower limbs were increased in 80% of the cases. Genetic analysis excluded the presence of pathological repeat expansions in spinocerebellar ataxia (SCA) types 1-3, 6-8, 10, 12 and 17, and DRPLA genes. Linkage exclusion tests showed no evidence of association with other known SCA loci. A genome-wide screen analysis identified linkage with chromosome 18 markers. A maximum two-point limit of determination score of 4.20 was found for marker D18S53. Haplotype analysis refined a critical region of 7.9 Mb between markers D18S1418 and D18S1104. This new SCA locus on 18p11.22-q11.2 has been designated SCA28. Candidate genes within the critical interval are currently screened for mutations.
Cagnoli
Claudia
C
Dipartimento di Genetica Biologia e Biochimica, Università degli Studi di Torino and S.C. Genetica Medica, Ospedale San Giovanni Battista di Torino, Torino, Italy.
Mariotti
Caterina
C
Taroni
Franco
F
Seri
Marco
M
Brussino
Alessandro
A
Michielotto
Chiara
C
Grisoli
Marina
M
Di Bella
Daniela
D
Migone
Nicola
N
Gellera
Cinzia
C
Di Donato
Stefano
S
Brusco
Alfredo
A
D000328:Adult; D001921:Brain / Q000473:pathology; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology
D005819:Genetic Markers