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Different phenotypes of Friedreich's ataxia within one 'pseudo-dominant' genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features.
Eur J Neurol. 2000 Sep; 7(5):535-40.EJ

Abstract

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.

Authors+Show Affiliations

Department of Neurogenetics, Institute of Neurology, Russian Academy of Medical Sciences, Moscow, Russia. neurogen@online.ruNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

11054139

Citation

Illarioshkin, S N., et al. "Different Phenotypes of Friedreich's Ataxia Within One 'pseudo-dominant' Genealogy: Relationships Between Trinucleotide (GAA) Repeat Lengths and Clinical Features." European Journal of Neurology, vol. 7, no. 5, 2000, pp. 535-40.
Illarioshkin SN, Bagieva GK, Klyushnikov SA, et al. Different phenotypes of Friedreich's ataxia within one 'pseudo-dominant' genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features. Eur J Neurol. 2000;7(5):535-40.
Illarioshkin, S. N., Bagieva, G. K., Klyushnikov, S. A., Ovchinnikov, I. V., Markova, E. D., & Ivanova-Smolenskaya, I. A. (2000). Different phenotypes of Friedreich's ataxia within one 'pseudo-dominant' genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features. European Journal of Neurology, 7(5), 535-40.
Illarioshkin SN, et al. Different Phenotypes of Friedreich's Ataxia Within One 'pseudo-dominant' Genealogy: Relationships Between Trinucleotide (GAA) Repeat Lengths and Clinical Features. Eur J Neurol. 2000;7(5):535-40. PubMed PMID: 11054139.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Different phenotypes of Friedreich's ataxia within one 'pseudo-dominant' genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features. AU - Illarioshkin,S N, AU - Bagieva,G K, AU - Klyushnikov,S A, AU - Ovchinnikov,I V, AU - Markova,E D, AU - Ivanova-Smolenskaya,I A, PY - 2000/10/29/pubmed PY - 2001/2/28/medline PY - 2000/10/29/entrez SP - 535 EP - 40 JF - European journal of neurology JO - Eur J Neurol VL - 7 IS - 5 N2 - 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. SN - 1351-5101 UR - https://www.unboundmedicine.com/medline/citation/11054139/Different_phenotypes_of_Friedreich's_ataxia_within_one_'pseudo_dominant'_genealogy:_relationships_between_trinucleotide__GAA__repeat_lengths_and_clinical_features_ L2 - https://doi.org/10.1046/j.1468-1331.2000.t01-1-00113.x DB - PRIME DP - Unbound Medicine ER -