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Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies.
Am J Med Genet. 1998 Oct 12; 79(5):396-9.AJ

Abstract

Approximately 95% of all Friedreich's ataxia (FA) patients are homozygous for a large GAA triplet-repeat expansion in the first intron of the Friedreich's ataxia gene (FRDA). The remaining cases are expected to be compound heterozygous with a GAA expansion on one allele and a point mutation on the other. Generally, the clinical diagnostic profile in this group of patients is indistinguishable from that in classic FA patients with homozygous expansions. This study describes a mildly affected patient who presents with only one expanded allele by Southern blot analysis. Point mutation screening shows a single base change in FRDA exon 3 resulting in a nonconservative amino acid replacement in the N-terminal portion of the frataxin protein. Extended family studies show that two of the patient's sibs are carriers of the expanded allele and one is a carrier of the missense mutation. This case study demonstrates the benefits of implementing a combined Southern blot and point mutation diagnostic protocol for compound heterozygous patients. By identifying both mutations, this procedure confirms the diagnosis of FA in patients with an atypical disease course and allows for more complete family studies.

Authors+Show Affiliations

Department of Pathology, The Ohio State University, Columbus, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article

Language

eng

PubMed ID

9779809

Citation

Bartolo, C, et al. "Identification of a Missense Mutation in a Friedreich's Ataxia Patient: Implications for Diagnosis and Carrier Studies." American Journal of Medical Genetics, vol. 79, no. 5, 1998, pp. 396-9.
Bartolo C, Mendell JR, Prior TW. Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies. Am J Med Genet. 1998;79(5):396-9.
Bartolo, C., Mendell, J. R., & Prior, T. W. (1998). Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies. American Journal of Medical Genetics, 79(5), 396-9.
Bartolo C, Mendell JR, Prior TW. Identification of a Missense Mutation in a Friedreich's Ataxia Patient: Implications for Diagnosis and Carrier Studies. Am J Med Genet. 1998 Oct 12;79(5):396-9. PubMed PMID: 9779809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a missense mutation in a Friedreich's ataxia patient: implications for diagnosis and carrier studies. AU - Bartolo,C, AU - Mendell,J R, AU - Prior,T W, PY - 1998/10/21/pubmed PY - 2000/6/20/medline PY - 1998/10/21/entrez SP - 396 EP - 9 JF - American journal of medical genetics JO - Am J Med Genet VL - 79 IS - 5 N2 - Approximately 95% of all Friedreich's ataxia (FA) patients are homozygous for a large GAA triplet-repeat expansion in the first intron of the Friedreich's ataxia gene (FRDA). The remaining cases are expected to be compound heterozygous with a GAA expansion on one allele and a point mutation on the other. Generally, the clinical diagnostic profile in this group of patients is indistinguishable from that in classic FA patients with homozygous expansions. This study describes a mildly affected patient who presents with only one expanded allele by Southern blot analysis. Point mutation screening shows a single base change in FRDA exon 3 resulting in a nonconservative amino acid replacement in the N-terminal portion of the frataxin protein. Extended family studies show that two of the patient's sibs are carriers of the expanded allele and one is a carrier of the missense mutation. This case study demonstrates the benefits of implementing a combined Southern blot and point mutation diagnostic protocol for compound heterozygous patients. By identifying both mutations, this procedure confirms the diagnosis of FA in patients with an atypical disease course and allows for more complete family studies. SN - 0148-7299 UR - https://www.unboundmedicine.com/medline/citation/9779809/Identification_of_a_missense_mutation_in_a_Friedreich's_ataxia_patient:_implications_for_diagnosis_and_carrier_studies_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0148-7299&date=1998&volume=79&issue=5&spage=396 DB - PRIME DP - Unbound Medicine ER -