Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

Puneeth H. Somashekar, Katta M. Girisha, Sheela Nampoothiri, Kalpana Gowrishankar, Radha R. Devi, Neerja Gupta, Dhanya L. Narayanan, Anupriya Kaur, Shruti Bajaj, Sujatha Jagadeesh, Leslie E.S. Lewis, Shenoy Shailaja, Anju Shukla

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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). Intra-familial 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.

Original languageEnglish
JournalClinical Genetics
DOIs
Publication statusPublished - 01-01-2019

Fingerprint

Waardenburg Syndrome
Hearing Loss
Albinism
Exome
Mosaicism
Genetic Heterogeneity
Neural Crest
Fathers
Cell Movement
Siblings
Phenotype

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Somashekar, Puneeth H. ; Girisha, Katta M. ; Nampoothiri, Sheela ; Gowrishankar, Kalpana ; Devi, Radha R. ; Gupta, Neerja ; Narayanan, Dhanya L. ; Kaur, Anupriya ; Bajaj, Shruti ; Jagadeesh, Sujatha ; Lewis, Leslie E.S. ; Shailaja, Shenoy ; Shukla, Anju. / Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome. In: Clinical Genetics. 2019.
@article{8e9e7960299c4856905f40096dc471be,
title = "Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome",
abstract = "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). Intra-familial 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.",
author = "Somashekar, {Puneeth H.} and Girisha, {Katta M.} and Sheela Nampoothiri and Kalpana Gowrishankar and Devi, {Radha R.} and Neerja Gupta and Narayanan, {Dhanya L.} and Anupriya Kaur and Shruti Bajaj and Sujatha Jagadeesh and Lewis, {Leslie E.S.} and Shenoy Shailaja and Anju Shukla",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/cge.13468",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",

}

Somashekar, PH, Girisha, KM, Nampoothiri, S, Gowrishankar, K, Devi, RR, Gupta, N, Narayanan, DL, Kaur, A, Bajaj, S, Jagadeesh, S, Lewis, LES, Shailaja, S & Shukla, A 2019, 'Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome', Clinical Genetics. https://doi.org/10.1111/cge.13468

Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome. / Somashekar, Puneeth H.; Girisha, Katta M.; Nampoothiri, Sheela; Gowrishankar, Kalpana; Devi, Radha R.; Gupta, Neerja; Narayanan, Dhanya L.; Kaur, Anupriya; Bajaj, Shruti; Jagadeesh, Sujatha; Lewis, Leslie E.S.; Shailaja, Shenoy; Shukla, Anju.

In: Clinical Genetics, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Locus and allelic heterogeneity and phenotypic variability in Waardenburg syndrome

AU - Somashekar, Puneeth H.

AU - Girisha, Katta M.

AU - Nampoothiri, Sheela

AU - Gowrishankar, Kalpana

AU - Devi, Radha R.

AU - Gupta, Neerja

AU - Narayanan, Dhanya L.

AU - Kaur, Anupriya

AU - Bajaj, Shruti

AU - Jagadeesh, Sujatha

AU - Lewis, Leslie E.S.

AU - Shailaja, Shenoy

AU - Shukla, Anju

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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). Intra-familial 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.

AB - 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). Intra-familial 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.

UR - http://www.scopus.com/inward/record.url?scp=85057346450&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057346450&partnerID=8YFLogxK

U2 - 10.1111/cge.13468

DO - 10.1111/cge.13468

M3 - Article

JO - Clinical Genetics

JF - Clinical Genetics

SN - 0009-9163

ER -