title: Spinocerebellar ataxia type 28.
abstract: We have recently mapped the spinocerebellar ataxia type 28 (SCA28) locus on chromosome 18p11.22 in a four-generation Italian family. The clinical phenotype in affected individuals of this family was characterized by juvenile onset, slowly progressive gait and limb ataxia, dysarthria, hyperreflexia at lower limbs, nystagmus, and ophthalmoparesis. The mean age at onset was 19.5 years, and no evidence of anticipation between generations was observed. The disease locus on chromosome 18p11.22-q11.2 was found to span a region of 7.9 Mb of genomic DNA. Direct sequencing of candidate genes within the critical interval led to the identification of a heterozygous point mutation in one of them. The mutation was located in a highly conserved domain with proposed functional properties in the protein product of the SCA28 gene, and segregated with the disease phenotype in all affected members of this family. Further genetic screening in 105 patients with autosomal dominant spinocerebellar ataxia negative for mutations in known SCA genes allowed the identification of a distinct missense mutation in a second Italian family. Both mutations are associated with amino acid changes in evolutionarily conserved residues of the alleged SCA28 gene, and indicate SCA28 as the sixth recognized SCA genotype caused by point mutations.
authors.affiliation: Unitâ di Genetica delle Malattie Neurodegenerative e Metaboliche, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Mariotti
authors.forename: Daniela Di
authors.initials: DD
authors.lastname: Bella
authors.forename: Stefano
authors.initials: S
authors.lastname: Di Donato
authors.forename: Franco
authors.initials: F
authors.lastname: Taroni
mesh_terms: D049069:ATP-Dependent Proteases / Q000235:genetics*; D000074183:ATPases Associated with Diverse Cellular Activities; D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D005192:Family Health; D005260:Female; D006801:Humans; D007558:Italy; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020754:Spinocerebellar Ataxias / Q000151:congenital; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult
chemical_list: D049069:ATP-Dependent Proteases; C120699:AFG3L2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities