Evento
Pathogenicity prediction for novel genetic variants related to hearing loss in a cohort of patients from Argentina
Buonfiglio, Paula Inés
; Bruque, Carlos David
; Lotersztein, Vanesa; Menazzi, Sebastián; Francipane, Liliana; Paoli, Bibiana Patricia; Elgoyhen, Ana Belen
; Dalamon, Viviana Karina
Tipo del evento:
Conferencia
Nombre del evento:
55th European Society of Human Genetics (ESHG) Conference
Fecha del evento:
11/06/2022
Institución Organizadora:
European Society of Human Genetics;
Título de la revista:
European Journal of Human Genetics
Editorial:
Nature Publishing Group
ISSN:
1018-4813
e-ISSN:
1476-5438
Idioma:
Inglés
Clasificación temática:
Resumen
Hearing loss (HL) is the most common disorder affecting 1:500 newborn children. Identification of causative mutations is demanding due to the more than 100 genes involved. Whole-exome sequencing (WES) has become a cost-effective approach for molecular diagnosis. However, the follow-up of novel variants, in particular missense changes, which can lead to a spectrum of phenotypes and unequivocal genotype-to-phenotype correlations, is not always straightforward. In this study, we investigated the genetic cause of sensorineural hearing loss in severe/profound deafness patients. After the exclusion of frequent GJB2-GJB6 mutations by Sanger Sequencing, we performed WES in 32 unrelated Argentinean families. Mutations were detected in 16 known deafness genes in 20 patients: ACTG1, ADGRV1 (GPR98), CDH23, COL4A3, COL4A5, DFNA5 (GSDDE), EYA4, LARS2, LOXHD1, MITF, MYO6, MYO7A, TECTA, TMPRSS3, USH2A and WSF1. Notably, 11 variants affecting 9 different non-GJB2 genes resulted novel: c.12829C>T, p.(Arg4277*) in ADGRV1; c.337del, p.(Asp109*) and c.3352del, p.(Gly1118Alafs*7) in CDH23; c.3500G>A, p.(Gly1167Glu) in COL4A3; c.1183C>T, p.(Pro395Ser) and c.1759C>T, p.(Pro587Ser) in COL4A5; c.580+2T>C in EYA4; c.1481dup, p.(Leu495Profs*31) in LARS2; c.1939T>C, p.(Phe647Leu) in MYO6; c.733C>T, p.(Gln245*) in MYO7A and c.242C>G, p.(Ser81*) in TMPRSS3 genes. To predict the effect of these variants, novel protein modeling and protein stability analysis were employed. These results highlight the value of WES to identify candidate variants, as well as bioinformatic strategies to infer their pathogenicity.
Palabras clave:
DEAFNESS
,
GENETIC VARIANTS
,
WES
,
BIOINFORMATICS
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(INGEBI)
Eventos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Eventos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Citación
Pathogenicity prediction for novel genetic variants related to hearing loss in a cohort of patients from Argentina; 55th European Society of Human Genetics (ESHG) Conference; Viena; Austria; 2022; 106-106
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