Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage‑hair hypoplasia syndrome in brazilian patients

Abstract

Produção científica do Laboratório de Hanseníase.This study was partially supported by funds from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq—INAGEMP (465549/2014-4).Coordenação de Aperfeiçoamento de Pessoal de Nível Superior- CAPES—INAGEMP (88887.136366/2017–00) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul—FAPERGS—INAGEMP (17/2551-0000521-0).Maria Eduarda Gomes was supported by fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and Fundação para o Desenvolvimento Científico e Tecnológico em Saúde—FIOTEC (VPPCB-002-FIO-22).Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin