Deafness_IsolatedAndComplex

Gene: KITLG

Green List (high evidence)

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

• PMID: 35543077
• 28504826
• 19375057
• 21368769

Mode of pathogenicity
Other

I don't know

Two unrelated families, limited functional data.
Sources: Expert list

Created: 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

• 26522471