Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

Somashekar, Puneeth H and Girisha, KM and Lewis, Leslie and Shenoy, Shailaja and Shukla, Anju (2018) Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome. Clinical Genetics. pp. 1-5. ISSN 0009-9163

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Waardenburg syndrome (WS) is a disorder of neural crest cell migration characterized by auditory and pigmentary abnormalities. We investigated a cohort of 14 families (16 subjects) either by targeted sequencing or whole-exome sequencing. Thirteen of these families were clinically diagnosed with WS and one family with isolated non-syndromic hearing loss (NSHL). Intrafamilial phenotypic variability and non-penetrance were observed in families diagnosed with WS1, WS2 and WS4 with pathogenic variants in PAX3, MITF and EDNRB, respectively. We observed gonosomal mosaicism for a variant in PAX3 in an asymptomatic father of two affected siblings. For the first time, we report a biallelic pathogenic variant in MITF in a subject with WS2 and a biallelic variant in EDNRB was noted in a subject with WS2. An individual with isolated NSHL carried a pathogenic variant in MITF. Blended phenotype of NSHL and albinism was observed in a subject clinically diagnosed to have WS2. A phenocopy of WS1 was observed in a subject with a reported pathogenic variant in GJB2, known to cause isolated NSHL. These novel and infrequently reported observations exemplify the allelic and genetic heterogeneity and show phenotypic diversity of WS.

Item Type: Article
Uncontrolled Keywords: DNA copy number variation; hearing loss; heterochromia iridis; Hirschsprung disease; mosaicism; penetrance; phenotypic variability; Waardenburg syndrome.
Subjects: Medicine > KMC Manipal > Medical Genetics
Medicine > KMC Manipal > Ophthalmology
Medicine > KMC Manipal > Paediatrics
Depositing User: KMC Library
Date Deposited: 17 Jan 2019 10:35
Last Modified: 12 May 2022 09:35

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