Artículo
Predicting pathogenicity for novel hearing loss mutations based on genetic and protein structure approaches
Buonfiglio, Paula Inés
; Bruque, Carlos David
; Lotersztein, Vanesa; Luce, Leonela Natalia
; Giliberto, Florencia
; Menazzi, Sebastián; Francipane, Liliana; Paoli, Bibiana Patricia; Goldschmidt, Ernesto; Elgoyhen, Ana Belen
; Dalamon, Viviana Karina
Fecha de publicación:
12/2022
Editorial:
Nature
Revista:
Scientific Reports
ISSN:
2045-2322
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Hearing loss is a heterogeneous disorder. Identification of causative mutations is demanding due to genetic heterogeneity. In this study, we investigated the genetic cause of sensorineural hearing loss in patients with severe/profound deafness. After the exclusion of GJB2-GJB6 mutations, we performed whole exome sequencing 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 + 2 T > C in EYA4; c.1481dup, p.(Leu495Profs*31) in LARS2; c.1939 T > 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 whole exome sequencing to identify candidate variants, as well as bioinformatic strategies to infer their pathogenicity.
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Articulos(INGEBI)
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos de INST.DE INVEST.EN ING.GENETICA Y BIOL.MOLECULAR "DR. HECTOR N TORRES"
Articulos(INIGEM)
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Articulos de INSTITUTO DE INMUNOLOGIA, GENETICA Y METABOLISMO
Citación
Buonfiglio, Paula Inés; Bruque, Carlos David; Lotersztein, Vanesa; Luce, Leonela Natalia; Giliberto, Florencia; et al.; Predicting pathogenicity for novel hearing loss mutations based on genetic and protein structure approaches; Nature; Scientific Reports; 12; 1; 12-2022; 1-14
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