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Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients.
Hum Genet. 2000 Jan; 106(1):86-92.HG

Abstract

Friedreich's ataxia is caused by mutations in the FRDA gene that encodes frataxin, a nuclear-encoded mitochondrial protein. Most patients are homozygous for the expansion of a GAA triplet repeat within the FRDA gene, but a few patients show compound heterozygosity for a point mutation and the GAA-repeat expansion. We analyzed DNA samples from a cohort of 241 patients with autosomal recessive or isolated spinocerebellar ataxia for the GAA triplet expansion. Patients heterozygous for the GAA expansion were screened for point mutations within the FRDA coding region. Molecular analyses included the single-strand conformation polymorphism analysis, direct sequencing, and linkage analysis with FRDA locus flanking markers. Seven compound heterozygous patients were identified. In four patients, a point mutation that predicts a truncated frataxin was detected. Three of them associated classic early-onset Friedreich's ataxia with an expanded GAA allele greater than 800 repeats. The other patient associated late-onset disease at the age of 29 years with a 350-GAA repeat expansion. In two patients manifesting the classical phenotype, no changes were observed by single-strand conformation polymorphism (SSCP) analysis. Linkage analysis in a family with two children affected by an ataxic syndrome, one of them showing heterozygosity for the GAA expansion, confirmed no linkage to the FRDA locus. Most point mutations in compound heterozygous Friedreich's ataxia patients are null mutations. In the present patients, clinical phenotype seems to be related to the GAA repeat number in the expanded allele. Complete molecular definition in these patients is required for clinical diagnosis and genetic counseling.

Authors+Show Affiliations

Unitat de Genètica, Hospital Universitari La Fe, Valencia, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10982187

Citation

De Castro, M, et al. "Genotype and Phenotype Analysis of Friedreich's Ataxia Compound Heterozygous Patients." Human Genetics, vol. 106, no. 1, 2000, pp. 86-92.
De Castro M, García-Planells J, Monrós E, et al. Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients. Hum Genet. 2000;106(1):86-92.
De Castro, M., García-Planells, J., Monrós, E., Cañizares, J., Vázquez-Manrique, R., Vílchez, J. J., Urtasun, M., Lucas, M., Navarro, G., Izquierdo, G., Moltó, M. D., & Palau, F. (2000). Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients. Human Genetics, 106(1), 86-92.
De Castro M, et al. Genotype and Phenotype Analysis of Friedreich's Ataxia Compound Heterozygous Patients. Hum Genet. 2000;106(1):86-92. PubMed PMID: 10982187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genotype and phenotype analysis of Friedreich's ataxia compound heterozygous patients. AU - De Castro,M, AU - García-Planells,J, AU - Monrós,E, AU - Cañizares,J, AU - Vázquez-Manrique,R, AU - Vílchez,J J, AU - Urtasun,M, AU - Lucas,M, AU - Navarro,G, AU - Izquierdo,G, AU - Moltó,M D, AU - Palau,F, PY - 2000/9/12/pubmed PY - 2000/9/30/medline PY - 2000/9/12/entrez SP - 86 EP - 92 JF - Human genetics JO - Hum Genet VL - 106 IS - 1 N2 - Friedreich's ataxia is caused by mutations in the FRDA gene that encodes frataxin, a nuclear-encoded mitochondrial protein. Most patients are homozygous for the expansion of a GAA triplet repeat within the FRDA gene, but a few patients show compound heterozygosity for a point mutation and the GAA-repeat expansion. We analyzed DNA samples from a cohort of 241 patients with autosomal recessive or isolated spinocerebellar ataxia for the GAA triplet expansion. Patients heterozygous for the GAA expansion were screened for point mutations within the FRDA coding region. Molecular analyses included the single-strand conformation polymorphism analysis, direct sequencing, and linkage analysis with FRDA locus flanking markers. Seven compound heterozygous patients were identified. In four patients, a point mutation that predicts a truncated frataxin was detected. Three of them associated classic early-onset Friedreich's ataxia with an expanded GAA allele greater than 800 repeats. The other patient associated late-onset disease at the age of 29 years with a 350-GAA repeat expansion. In two patients manifesting the classical phenotype, no changes were observed by single-strand conformation polymorphism (SSCP) analysis. Linkage analysis in a family with two children affected by an ataxic syndrome, one of them showing heterozygosity for the GAA expansion, confirmed no linkage to the FRDA locus. Most point mutations in compound heterozygous Friedreich's ataxia patients are null mutations. In the present patients, clinical phenotype seems to be related to the GAA repeat number in the expanded allele. Complete molecular definition in these patients is required for clinical diagnosis and genetic counseling. SN - 0340-6717 UR - https://www.unboundmedicine.com/medline/citation/10982187/Genotype_and_phenotype_analysis_of_Friedreich's_ataxia_compound_heterozygous_patients_ L2 - https://dx.doi.org/10.1007/s004399900201 DB - PRIME DP - Unbound Medicine ER -