Frequency and Genetic Profile of Compound Heterozygous Friedreich’s Ataxia Patients—the Brazilian Experience
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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.
KeywordsCompound heterozygous Friedreich’s ataxia FRDA mutation Genetic counseling
This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo- FAPESPs (grant no. 2013/01766-7).
Compliance with Ethical Standards
This study was approved by the Research Ethics Committee of each center. Each subject signed an informed consent before genetic testing.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 1.Fussiger H, Saraiva-Pereira ML, Leistner-Segal S, Jardim LB. Friedreich ataxia: diagnostic yield and minimal frequency in South Brazil. Cerebellum. 2018;1–5.Google Scholar
- 10.Brazilian Initiative on Precision Medicine BIPMed. [cited 2018 November 29]. Available from: http://bipmed.iqm.unicamp.br/genes.
- 14.Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–23.CrossRefGoogle Scholar