| First Author | Yue Q | Year | 1997 |
| Journal | Am J Hum Genet | Volume | 61 |
| Issue | 5 | Pages | 1078-87 |
| PubMed ID | 9345107 | Mgi Jnum | J:44367 |
| Mgi Id | MGI:1099949 | Doi | 10.1086/301613 |
| Citation | Yue Q, et al. (1997) Progressive ataxia due to a missense mutation in a calcium-channel gene. Am J Hum Genet 61(5):1078-87 |
| abstractText | We describe a family with severe progressive cerebellar ataxia involving the trunk, the extremities, and speech. The proband, who has prominent atrophy of the cerebellum, shown by magnetic resonance imaging, was confined to a wheelchair at the age of 44 years. Two sons have episodes of vertigo and ataxia that are not responsive to acetazolamide. Quantitative eye-movement testing showed a consistent pattern of abnormalities localizing to the cerebellum. Genotyping suggested linkage to chromosome 19p, and SSCP showed an aberrant migrating fragment in exon 6 of the calcium-channel gene CACNA1A, which cosegregated with the disease. Sequencing of exon 6 identified a G-->A transposition in one allele, at nucleotide 1152, resulting in a predicted glycine-to-arginine substitution at codon 293. The CAG-repeat expansion associated with spinocerebellar ataxia 6 was not present in any family members. This family is unique in having a non-CAG-repeat mutation that leads to severe progressive ataxia. Since a great deal is known about the function of calcium channels, we speculate on how this missense mutation leads to the combination of clinical symptoms and signs. |
