We examined a large Turkmen family with 'pseudo-dominant' inheritance of Friedreich's ataxia resulting from consanguineous marriage of a Friedreich's ataxia patient to a heterozygote carrying an ancestral mutated allele. Two distinct phenotypes of the disease co-segregated within this genealogy. Two brothers from the younger generation exhibited 'classical' Friedreich's ataxia with onset of symptoms before 10 years and a rapidly progressive course. In contrast, three patients (two sisters from the younger generation and their father) had a more benign phenotype of late-onset Friedreich's ataxia with the onset at 26, 45 and 48 years and slow progression over decades. The patients with 'classical' Friedreich's ataxia were homozygous for a common ancestral expanded allele of the X25 gene containing 700-800 GAA repeats, while the patients with late-onset Friedreich's ataxia had two different mutated alleles, the shorter 250-repeat expansion of paternal origin and the longer 700-repeat expansion of maternal origin. One may conclude that clinical variability of Friedreich's ataxia in our patients is accounted for predominantly by a modifying effect of one of the two (shorter or longer) expanded alleles inherited from their affected father. Our observation clearly demonstrates the significance of variable-sized alleles for the phenotypic expression of the disease.

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Материалы и методы. Были обследованы 285 российских пациентов с боковым амиотрофическим склерозом (БАС), -represented -38.0 % vs. 26.6 % (χ 2 = 13.17; р = 0.002

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