info:eu-repo/semantics/publishedVersion
Large-scale molecular analysis of hereditary hearing loss genes in argentinean deaf patients: lookingfora needle in a haystack
Fecha
2019Registro en:
Large-scale molecular analysis of hereditary hearing loss genes in argentinean
deaf patients: lookingfora needle in a haystack; 51st European Society of Human Genetics Conference; Milan; Italia; 2018; 1-1
1018-4813
1476-5438
CONICET Digital
CONICET
Autor
Buonfiglio, Paula Inés
Bruque, Carlos David
Lotersztein, Vanesa
Goldschmidt, E.
Elgoyhen, Ana Belen
Dalamon, Viviana Karina
Resumen
Hereditary Hearing Loss (HHL) is a common trait affecting 1 in 2000 new born children. The presence of over 100 different genes involved in HHL, lead us to go on board with Whole Exome Sequencing (WES) in order to search for the causative mutations.The main objective of this project was to diagnose Argentinean deaf families and discover novel mutations or new genes involved in pathology.We designed a flowchart to exclude all the spurious variations obtained and target for few candidates. To approach this, we filtered results, and candidate variations were segregated throughout family members. Variations positively selected, were analyzed using bioinformatic predictors and tracked in public databases. Additionally, conservation studies, structure and functional domain analysis in proteins, and in-vivo studies were performed.Using this strategy we analysed 15 WES results. We identified 16 causative mutations in 12 families with syndromic and non-syndromic hearing loss (11 missense, 4 frameshift and 1 splicing site mutations). Six were novel and functional studies of some of the identified mutations, using Zebra fish models, are under way. In the remaining 3 families, variables of uncertain significance were detected (Vous).To our knowledge this is the first study using WES to diagnose deaf patients in Argentina. We show in the present study that our flowchart is advantageous and noteworthy for large-scale molecular analysis in deaf patients. These findings clearly highlight the importance of genetic studies followed by in-sílico and in-vivo validation to better understand the genetic basis of Hereditary Hearing loss.