Deafness_IsolatedAndComplex
Gene: KITLG
PMID: 35543077:
- Six unrelated children with homozygous variants and features consistent with WS2. All six probands had sensorineural hearing loss and pigmentary abnormalities of the hair and skin, and five also had pigmentary changes of the iris. Heterozygous parents were unaffected.
PMID: 28504826:
- A 16-year-old boy with Waardenburg syndrome type 2F manifested as sensorineural deafness, brilliant blue irises, and hypopigmentation of the lower extremities, had homozygosity for a missense variant that segregated with disease in the family.
PMID: 19375057:
- Gain of function missense variant identified in one family with multiple affected individuals with familial progressive hyperpigmentation. The variant segregated with disease perfectly.
PMID: 21368769:
- Three different mutations in four families with familial progressive hyper- and hypopigmentation.
AD Deafness remains amber (as per previous review). Two families with reduced penetrance reported.
Genotype phenotype correlation:
- Gain-of-function variants are associated with familial progressive hyperpigmentation and hyper- and hypopigmentation
- Postulated that biallelic loss-of-function variants cause generalized hypomelanosis while variants with residual protein function lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss mostly reminiscent of WS2 or piebaldism.Created: 14 Jul 2022, 2:07 a.m. | Last Modified: 14 Jul 2022, 2:07 a.m.
Panel Version: 1.137
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
deafness; heterochromia iridis; hypopigmentation of the skin; hyperpigmentation of the skin; Waardenburg syndrome
Publications
Mode of pathogenicity
Other
Two unrelated families, limited functional data.
Sources: Expert listCreated: 31 Dec 2019, 1:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Publications
Phenotypes for gene: KITLG were changed from Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 to Waardenburg syndrome, MONDO:0018094, KITLG-related; Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697
Mode of inheritance for gene: KITLG was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: kitlg has been classified as Green List (High Evidence).
Gene: kitlg has been classified as Amber List (Moderate Evidence).
Gene: kitlg has been classified as Amber List (Moderate Evidence).
gene: KITLG was added gene: KITLG was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert list Mode of inheritance for gene: KITLG was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KITLG were set to 26522471 Phenotypes for gene: KITLG were set to Deafness, autosomal dominant 69, unilateral or asymmetric, MIM# 616697 Review for gene: KITLG was set to AMBER