Homozygosity mapping of spinocerebellar ataxia with cerebellar atrophy andperipheral neuropathy to 9q33-34, and with hearing impairment and optic atrophy to 6p21-23

With the availability of a simple molecular test that distinguishes Friedre ich ataxia, the most frequent form of inherited ataxia, from other recessiv e ataxias, it now becomes possible to unravel the genetic heterogeneity of the latter. We have now localised two genes causing autosomal recessive spi nocerebellar ataxia in two consanguineous families. In the first family, th e four affected Japanese sibs had spinocerebellar ataxia associated with el evated levels of serum creatine kinase, gamma -globulin, and or-foetoprotei n. Homozygosity over a 20 cM region allowed to demonstrate linkage at 9q33. 3-34.3 with a lod score of 3.0. Genotyping two unrelated Japanese patients from first degree consanguineous parents revealed that one was homozygous f or the same region but did not share the biochemical features. In the secon d family, an Israeli uncle and a niece were affected by an early-onset rece ssive ataxia and subsequently developed hearing impairment and optic atroph y. Homozygosity over a 17 cM region allowed demonstration of linkage at 6p2 1-23 with a rod score of 3.25. These two localisations of autosomal recessi ve ataxia genes represent a first step toward the identification of genetic ally homogenous, non-friedreich, ataxic patients and subsequent cloning of the genes.