Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.
Journal
Journal of the European Academy of Dermatology and Venereology : JEADV
ISSN: 1468-3083
Titre abrégé: J Eur Acad Dermatol Venereol
Pays: England
ID NLM: 9216037
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
11
12
2021
accepted:
21
04
2022
pubmed:
12
5
2022
medline:
23
8
2022
entrez:
11
5
2022
Statut:
ppublish
Résumé
Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. To describe the genotypic and clinical spectrum of biallelic KITLG-variants. We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.
Sections du résumé
BACKGROUND
BACKGROUND
Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner.
OBJECTIVES
OBJECTIVE
To describe the genotypic and clinical spectrum of biallelic KITLG-variants.
METHODS
METHODS
We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports.
RESULTS
RESULTS
We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism.
CONCLUSIONS
CONCLUSIONS
We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.
Identifiants
pubmed: 35543077
doi: 10.1111/jdv.18207
pmc: PMC9546089
doi:
Substances chimiques
KITLG protein, human
0
Stem Cell Factor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1606-1611Subventions
Organisme : Bio-CARe Woman Scientist Award, Department of Biotechnology, Ministry of Science and Technology, Government of India
ID : BT/Bio-CARe/07/ 9889/2013-14
Organisme : Deutsche Forschungsgemeinschaft
ID : Collaborative Research Center 889
Organisme : John T. and Winifred M. Hayward Foundation
Informations de copyright
© 2022 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
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