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Cerebellum. 2019 Jun 26. doi: 10.1007/s12311-019-01055-z. [Epub ahead of print]

Frequency and Genetic Profile of Compound Heterozygous Friedreich's Ataxia Patients-the Brazilian Experience.

Author information

1
Department of Medical Genetics and Genomic Medicine, School of Medicine, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, 13083-887, Brazil.
2
Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-003, Brazil.
3
Department of Neurosciences and Behavior Sciences, Ribeirão Preto School of Medicine, University of São Paulo (HCFMRP-USP), Campus Universitário s/n Monte Alegre, Ribeirão Preto, SP, 14048-900, Brazil.
4
Department of Neurology, School of Medicine, University of Campinas - UNICAMP, Rua Tessália Vieira de Camargo, 126, Cidade Universitaria "Zeferino Vaz", Campinas, SP, 13083-887, Brazil. mcfrancajr@uol.com.br.

Abstract

Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia in Caucasian populations. It is caused by a homozygous GAA expansion in the first intron of the frataxin gene (FXN) (OMIM: 606829) in 96% of the affected individuals. The remaining patients have a GAA expansion in one allele and a point mutation in the other. Little is known about compound heterozygous patients outside Europe and North America. We have thus designed a study to determine the frequency and mutational profile of these patients in Brazil. To accomplish that, we recruited all patients with ataxia and at least one expanded GAA allele at FXN from 3 national reference centers. We identified those subjects with a single expansion and proceeded with further genetic testing (Sanger sequencing and CGH arrays) for those. There were 143 unrelated patients (128 families), five of which had a single expanded allele. We identified point mutations in three out of these five (3/128 = 2.34%). Two patients had the c.157delC variant, whereas one individual had the novel variant c.482+1G>T. These results indicate that FXN point mutations are rare, but exist in Brazilian patients with FRDA. This has obvious implications for diagnostic testing and genetic counseling.

KEYWORDS:

Compound heterozygous; FRDA mutation; Friedreich’s ataxia; Genetic counseling

PMID:
31243663
DOI:
10.1007/s12311-019-01055-z

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