Archivio dell'Università Alfonso X El Sabio

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2

Mostra i principali dati dell'item

APA

Zazo Seco, Celia & Serrao de Castro, Luciana & van Nierop, Josephine W. & Morín, Matías & Jhangiani, Shalini & Verver, Eva J.J. & Schraders, Margit & Maiwald, Nadine & Wesdorp, Mieke & Venselaar, Hanka & Spruijt, Liesbeth & Oostrik, Jaap & Schoots, Jeroen & Baylor-Hopkins Center for Mendelian Genomics & van Reeuwijk, Jeroen & Lelieveld, Stefan H. & Huygen, Patrick L.M. & Insenser, María & Admiraal, Ronald J.C. & Pennings, Ronald J.E. & Hoefsloot, Lies H. & Arias Vásquez, Alejandro & de Ligt, Joep & Yntema, Helger G. & Jansen, Joop H. & Muzny, Donna M. & Huls, Gerwin & van Rossum, Michelle M. & Lupski, James R. & Moreno Pelayo, Miguel Angel & Kunst, Henricus P.M. & Kremer, Hannie (2015-11 ) .Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

ISO 690

Zazo Seco, Celia & Serrao de Castro, Luciana & van Nierop, Josephine W. & Morín, Matías & Jhangiani, Shalini & Verver, Eva J.J. & Schraders, Margit & Maiwald, Nadine & Wesdorp, Mieke & Venselaar, Hanka & Spruijt, Liesbeth & Oostrik, Jaap & Schoots, Jeroen & Baylor-Hopkins Center for Mendelian Genomics & van Reeuwijk, Jeroen & Lelieveld, Stefan H. & Huygen, Patrick L.M. & Insenser, María & Admiraal, Ronald J.C. & Pennings, Ronald J.E. & Hoefsloot, Lies H. & Arias Vásquez, Alejandro & de Ligt, Joep & Yntema, Helger G. & Jansen, Joop H. & Muzny, Donna M. & Huls, Gerwin & van Rossum, Michelle M. & Lupski, James R. & Moreno Pelayo, Miguel Angel & Kunst, Henricus P.M. & Kremer, Hannie. 2015-11 .Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

https://hdl.handle.net/20.500.12080/39722
dc.contributor.author Zazo Seco, Celia
dc.contributor.author Serrao de Castro, Luciana
dc.contributor.author van Nierop, Josephine W.
dc.contributor.author Morín, Matías
dc.contributor.author Jhangiani, Shalini
dc.contributor.author Verver, Eva J.J.
dc.contributor.author Schraders, Margit
dc.contributor.author Maiwald, Nadine
dc.contributor.author Wesdorp, Mieke
dc.contributor.author Venselaar, Hanka
dc.contributor.author Spruijt, Liesbeth
dc.contributor.author Oostrik, Jaap
dc.contributor.author Schoots, Jeroen
dc.contributor.author Baylor-Hopkins Center for Mendelian Genomics
dc.contributor.author van Reeuwijk, Jeroen
dc.contributor.author Lelieveld, Stefan H.
dc.contributor.author Huygen, Patrick L.M.
dc.contributor.author Insenser, María
dc.contributor.author Admiraal, Ronald J.C.
dc.contributor.author Pennings, Ronald J.E.
dc.contributor.author Hoefsloot, Lies H.
dc.contributor.author Arias Vásquez, Alejandro
dc.contributor.author de Ligt, Joep
dc.contributor.author Yntema, Helger G.
dc.contributor.author Jansen, Joop H.
dc.contributor.author Muzny, Donna M.
dc.contributor.author Huls, Gerwin
dc.contributor.author van Rossum, Michelle M.
dc.contributor.author Lupski, James R.
dc.contributor.author Moreno Pelayo, Miguel Angel
dc.contributor.author Kunst, Henricus P.M.
dc.contributor.author Kremer, Hannie
dc.date.accessioned 2024-02-12T14:33:33Z
dc.date.available 2024-02-12T14:33:33Z
dc.date.created 2015-11
dc.date.issued 2015-11
dc.identifier.uri https://hdl.handle.net/20.500.12080/39722
dc.description.abstract Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mu tation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlyingWS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants. es_ES
dc.format application/pdf es_ES
dc.language eng es_ES
dc.rights CC-BY es_ES
dc.rights.uri http://creativecommons.org/licenses/by/4.0/deed.es es_ES
dc.title Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2 es_ES
dc.type info:eu-repo/semantics/article es_ES
dc.rights.accessrights info:eu-repo/semantics/openAccess es_ES
dc.identifier.location N/A es_ES


Files in questo item

Questo item appare nelle seguenti collezioni

Mostra i principali dati dell'item

CC-BY Except where otherwise noted, this item's license is described as CC-BY

Cerca in DSpace


Ricerca

My Account

Social Media