Author:
Gomes Maria Eduarda,Kehdy Fernanda,de Neves-Manta Fernanda Saloum,Horovitz Dafne Dain Gandelman,Sanseverino Maria Teresa,Leal Gabriela Ferraz,Felix Têmis Maria,Cavalcanti Denise Pontes,Llerena Juan Clinton,Gonzalez Sayonara
Abstract
AbstractCartilage-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.
Funder
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil
Fundação para o Desenvolvimento Científico e Tecnológico em Saúde - FIOTEC
Publisher
Springer Science and Business Media LLC
Reference35 articles.
1. McKusick, V. A., Eldrige, R., Hostetler, J. A., Ruangwit, U. & Egeland, J. A. Dwarfism in the Amish. II. Cartilage-hair hypoplasia. Bull. Johns Hopkins Hosp. 116, 285–326 (1965).
2. Mäkitie, O., Tapanainen, P. J., Dunkel, L. & Siimes, M. A. Impaired spermatogenesis: An unrecognized feature of cartilage-hair hypoplasia. Ann. Med. 33(3), 201–205 (2001).
3. Williams, M. S. et al. The natural history of severe anemia in cartilage-hair hypoplasia. Am. J. Med. Genet. A 138(1), 35–40 (2005).
4. Kavadas, F. D. et al. Variability of clinical and laboratory features among patients with ribonuclease mitochondrial RNA processing endoribonuclease gene mutations. J. Allergy Clin. Immunol. 122(6), 1178–1184 (2008).
5. Ip, W. et al. Variable phenotype of severe immunodeficiencies associated with RMRP gene mutations. J. Clin. Immunol. 35(2), 147–157 (2015).