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

Overview of attention for article published in American Journal of Human Genetics, November 2015
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  • Good Attention Score compared to outputs of the same age (68th percentile)

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4 tweeters
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Citations

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54 Mendeley
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Title
Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2
Published in
American Journal of Human Genetics, November 2015
DOI 10.1016/j.ajhg.2015.09.011
Pubmed ID
Authors

Celia Zazo Seco, Luciana Serrão de Castro, Josephine W. van Nierop, Matías Morín, Shalini Jhangiani, Eva J.J. Verver, Margit Schraders, Nadine Maiwald, Mieke Wesdorp, Hanka Venselaar, Liesbeth Spruijt, Jaap Oostrik, Jeroen Schoots, Jeroen van Reeuwijk, Stefan H. Lelieveld, Patrick L.M. Huygen, María Insenser, Ronald J.C. Admiraal, Ronald J.E. Pennings, Lies H. Hoefsloot, Alejandro Arias-Vásquez, Joep de Ligt, Helger G. Yntema, Joop H. Jansen, Donna M. Muzny, Gerwin Huls, Michelle M. van Rossum, James R. Lupski, Miguel Angel Moreno-Pelayo, Henricus P.M. Kunst, Hannie Kremer

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 mutation 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 underlying WS2 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Israel 1 2%
Unknown 53 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 17%
Researcher 8 15%
Student > Master 8 15%
Other 7 13%
Student > Bachelor 5 9%
Other 11 20%
Unknown 6 11%
Readers by discipline Count As %
Medicine and Dentistry 16 30%
Biochemistry, Genetics and Molecular Biology 12 22%
Agricultural and Biological Sciences 9 17%
Engineering 2 4%
Neuroscience 2 4%
Other 4 7%
Unknown 9 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 December 2015.
All research outputs
#5,049,193
of 16,534,657 outputs
Outputs from American Journal of Human Genetics
#2,655
of 4,930 outputs
Outputs of similar age
#88,395
of 288,175 outputs
Outputs of similar age from American Journal of Human Genetics
#34
of 41 outputs
Altmetric has tracked 16,534,657 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 4,930 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.5. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 288,175 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 68% of its contemporaries.
We're also able to compare this research output to 41 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.