Genetic Analysis of Hereditary Ataxias in Peru Identifies SCA10 Families with Incomplete Penetrance
Relative frequency of hereditary ataxias remains unknown in many regions of Latin America. We described the relative frequency in spinocerebellar ataxias (SCA) due to (CAG)n and to (ATTCT)n expansions, as well as Friedreich ataxia (FRDA), among cases series of ataxic individuals from Peru. Among ataxic index cases from 104 families (38 of them with and 66 without autosomal dominant pattern of inheritance), we identified 22 SCA10, 8 SCA2, 3 SCA6, 2 SCA3, 2 SCA7, 1 SCA1, and 9 FRDA cases (or families). SCA10 was by far the most frequent one. Findings in SCA10 and FRDA families were of note. Affected genitors were not detected in 7 out of 22 SCA10 nuclear families; then overall maximal penetrance of SCA10 was estimated as 85%; in multiplex families, penetrance was 94%. Two out of nine FRDA cases carried only one allele with a GAA expansion. SCA10 was the most frequent hereditary ataxia in Peru. Our data suggested that ATTCT expansions at ATXN10 might not be fully penetrant and/or instability between generations might frequently cross the limits between non-penetrant and penetrant lengths. A unique distribution of inherited ataxias in Peru requires specific screening panels, considering SCA10 as first line of local diagnosis guidelines.
KeywordsCAG repeats Friedreich ataxia Inherited ataxias Penetrance Peru Spinocerebellar ataxia
Authors would like to thank patients and families affected from inherited ataxias that kindly contributed to research on ataxias in Peruvian population. We would also thank Diego Veliz-Otani for critical review of the manuscript. We are grateful to RIBERMOV “Red Iberoamericana Multidisciplinar para el Estudio de los Trastornos de Movimiento” for providing the initial environment for collaborative research studies, as this one, among Latin Americans.
EPM, GVF, GBB, SLS, MLSP, and LBJ were supported by the National Council for Research and Development (CNPq), Brazil. LBJ received grants from Fundo de Incentivo à Pesquisa do Hospital de Clínicas de Porto Alegre (FIPE 2006-0384) and Pesquisa para o SUS/Fundo de Apoio à Pesquisa do Rio Grande do Sul, Brazil (PPSUS-FAPERGS, PROCESS 07-00832), for performing the laboratory procedures. MCO, MIM, VM, and PM are partially supported by research funds provided by Instituto Nacional de Ciencias Neurológicas.
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Conflict of Interest
The authors declare that they have no conflict of interest.
- 11.Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. - PubMed - NCBI [Internet]. [cited 2019 Nov 30]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/19429075.
- 22.Cornejo-Olivas M, Cornejo-Herrera I, Lindo-Samanamud S, Castilhos R, Saraiva-Pereira ML, Jardim L, et al. Spinocerebellar Ataxia Type 10 or SCA10 in Peruvian Population. First Report of Three Families (IN6–1.007). Neurology [Internet]. 2013 [cited 2019 Mar 7];80:IN6–1.007-IN6–1.007. Available from: https://n.neurology.org/content/80/7_Supplement/IN6-1.007.
- 32.Jonker MA, Rijken JA, Hes FJ, Putter H, Hensen EF. Estimating the penetrance of pathogenic gene variants in families with missing pedigree information. Stat Methods Med Res. 2018;962280218791338.Google Scholar