A family with pseudodominant Friedreich's ataxia showing marked variation of phenotype between affected siblings.

Abstract

A family with pseudodominant Friedreich's ataxia is described showing marked variation of phenotype between affected siblings. The mother of this family (III-3) developed a spastic ataxic tetraplegia with neuropathy at 34 years of age; her husband, who was unrelated, was clinically normal. Of their nine children, two (IV-2, IV-3), including one with multiple sclerosis (IV-3), developed a mild spinocerebellar degeneration in the third decade. Three in their late 20s had an asymptomatic spinocerebellar degeneration (IV-4, IV-5, IV-6) and one was confined to a wheelchair at 15 years with typical Friedreich's ataxia (IV-9). Three other siblings (IV-1, IV-7, IV-8) were clinically normal. The father proved to be heterozygous for the triplet repeat expansion at the Friedreich's ataxia locus and all clinically affected members were homozygous for alleles in the expanded size range. This family confirms that homozygote-heterozygote mating is the genetic basis for some families with apparent autosomal dominant Friedreich's ataxia.