Frequency and origin of the c.2090T > G p.(Leu697Trp) MYO3A variant associated with autosomal dominant hearing loss

Autor(es):Mostrar menos -

Bueno, Andre S. ^[1] ; Nunes, Kelly ^[1] ; Dias, Alex M. M. ^[1] ; Alves, Leandro U. ^[1] ; Mendes, Beatriz C. A. ^[2] ; Sampaio-Silva, Juliana ^[3] ; Smits, Jeroen ^{[4, 5]} ; Yntema, Helger G. ^[6] ; Meyer, Diogo ^[1] ; Lezirovitz, Karina ^{[1, 3]} ; Mingroni-Netto, Regina C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisas Genoma Humano & Celulas Tronco, Dept Genet & Biol Evolut, Sao Paulo - Brazil

^[2] Pontificia Univ Catolica Sao Paulo, Div Educ & Reabilitacao Disturbios Comunicacao, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Med, Hosp Clin, Lab Otorrinolaringol LIM32, Sao Paulo - Brazil

^[4] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Nijmegen - Netherlands

^[5] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, Nijmegen - Netherlands

^[6] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen - Netherlands

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Human Genetics; v. 30, n. 1, p. 13-21, JAN 2022.
• Citações Web of Science: 4

Resumo

We recently described a novel missense variant {[}c.2090T>G:p.(Leu697Trp)] in the MYO3A gene, found in two Brazilian families with late-onset autosomal dominant nonsyndromic hearing loss (ADNSHL). Since then, with the objective of evaluating its contribution to ADNSHL in Brazil, the variant was screened in additional 101 pedigrees with probable ADNSHL without conclusive molecular diagnosis. The variant was found in three additional families, explaining 3/101 (similar to 3%) of cases with ADNSHL in our Brazilian pedigree collection. In order to identify the origin of the variant, 21 individuals from the five families were genotyped with a high-density SNP array (similar to 600 K SNPs- Axiom Human Origins; ThermoFisher). The identity by descent (IBD) approach revealed that many pairs of individuals from the different families have a kinship coefficient equivalent to that of second cousins, and all share a minimum haplotype of similar to 607 kb which includes the c.2090T>G variant suggesting it probably arose in a common ancestor. We inferred that the mutation occurred in a chromosomal segment of European ancestry and the time since the most common ancestor was estimated in 1100 years (CI = 775-1425). This variant was also reported in a Dutch family, which shares a 87,121 bp haplotype with the Brazilian samples, suggesting that Dutch colonists may have brought it to Northeastern Brazil in the 17th century. Therefore, the present study opens new avenues to investigate this variant not only in Brazilians but also in European families with ADNSHL. (AU)

• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs