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

Autor(es)

Peluzzo, Thiago Mazzo ^[1] ; Bonadia, Luciana Cardoso ^[1] ; Donatti, Amanda ^[1] ; Molck, Miriam Coelho ^[1] ; Jardim, Laura Bannach ^[2] ; Marques, Jr., Wilson ^[3] ; Lopes-Cendes, Iscia Teresinha ^[1] ; Franca, Jr., Marcondes C. ^[4]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Dept Med Genet & Genom Med, Sch Med, Rua Tessalia Vieira de Camargo 126, BR-13083887 Campinas, SP - Brazil

^[2] Hosp Clin Porto Alegre, Med Genet Serv, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS - Brazil

^[3] Univ Sao Paulo HCFMRP USP, Ribeirao Preto Sch Med, Dept Neurosci & Behav Sci, Campus Univ S-N Monte Alegre, BR-14048900 Ribeirao Preto, SP - Brazil

^[4] Univ Campinas UNICAMP, Sch Med, Dept Neurol, Rua Tessalia Vieira de Camargo 126, BR-13083887 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CEREBELLUM; v. 18, n. 6, p. 1143-1146, DEC 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 13/01766-7 - Contribuição ao diagnóstico, à fisiopatologia e à terapêutica das neuronopatias sensitivas
• Beneficiário: Marcondes Cavalcante Franca Junior
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores