Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss

Memoona Ramzan, Hafiza Idrees, Ghulam Mujtaba, Nara Sobreira, P. Dane Witmer, Sadaf Naz

Research output: Contribution to journalArticle

Abstract

Variants of KCNQ4 are one of the most common causes of dominantly inherited nonsyndromic hearing loss. We investigated a consanguineous family in which two individuals had prelignual hearing loss, apparently inherited in a recessive mode. Whole-exome sequencing analyses demonstrated genetic heterogeneity as variants in two different genes segregated with the phenotype in two branches of the family. Members in one branch were homozygous for a pathogenic variant of TMC1. The other two affected individuals were homozygous for a missense pathogenic variant in KCNQ4 c.872C>T; p.(Pro291Leu). These two individuals had prelingual, progressive moderate to severe hearing loss, while a heterozygous carrier had late onset mild hearing loss. Our work demonstrates that p.Pro291L variant is semi-dominantly inherited. This is the first report of semi-dominance of a KCNQ4 variant.

Original languageEnglish (US)
Pages (from-to)109-112
Number of pages4
JournalGene
Volume705
DOIs
StatePublished - Jul 15 2019

Fingerprint

Hearing Loss
Exome
Genetic Heterogeneity
Phenotype
Genes

Keywords

  • ADNSHL
  • ARNSHL
  • Baylor-Hopkins Center for Mendelian Genomics
  • BHCMG
  • Deafness
  • DFNA2A
  • Hearing loss
  • KCNQ4
  • Pakistan
  • WES
  • Whole exome sequencing

ASJC Scopus subject areas

  • Genetics

Cite this

Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss. / Ramzan, Memoona; Idrees, Hafiza; Mujtaba, Ghulam; Sobreira, Nara; Witmer, P. Dane; Naz, Sadaf.

In: Gene, Vol. 705, 15.07.2019, p. 109-112.

Research output: Contribution to journalArticle

Ramzan, Memoona ; Idrees, Hafiza ; Mujtaba, Ghulam ; Sobreira, Nara ; Witmer, P. Dane ; Naz, Sadaf. / Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss. In: Gene. 2019 ; Vol. 705. pp. 109-112.
@article{c2fc3de8599e48ab9d39d69d5fe126b0,
title = "Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss",
abstract = "Variants of KCNQ4 are one of the most common causes of dominantly inherited nonsyndromic hearing loss. We investigated a consanguineous family in which two individuals had prelignual hearing loss, apparently inherited in a recessive mode. Whole-exome sequencing analyses demonstrated genetic heterogeneity as variants in two different genes segregated with the phenotype in two branches of the family. Members in one branch were homozygous for a pathogenic variant of TMC1. The other two affected individuals were homozygous for a missense pathogenic variant in KCNQ4 c.872C>T; p.(Pro291Leu). These two individuals had prelingual, progressive moderate to severe hearing loss, while a heterozygous carrier had late onset mild hearing loss. Our work demonstrates that p.Pro291L variant is semi-dominantly inherited. This is the first report of semi-dominance of a KCNQ4 variant.",
keywords = "ADNSHL, ARNSHL, Baylor-Hopkins Center for Mendelian Genomics, BHCMG, Deafness, DFNA2A, Hearing loss, KCNQ4, Pakistan, WES, Whole exome sequencing",
author = "Memoona Ramzan and Hafiza Idrees and Ghulam Mujtaba and Nara Sobreira and Witmer, {P. Dane} and Sadaf Naz",
year = "2019",
month = "7",
day = "15",
doi = "10.1016/j.gene.2019.04.064",
language = "English (US)",
volume = "705",
pages = "109--112",
journal = "Gene",
issn = "0378-1119",
publisher = "Elsevier",

}

TY - JOUR

T1 - Bi-allelic Pro291Leu variant in KCNQ4 leads to early onset non-syndromic hearing loss

AU - Ramzan, Memoona

AU - Idrees, Hafiza

AU - Mujtaba, Ghulam

AU - Sobreira, Nara

AU - Witmer, P. Dane

AU - Naz, Sadaf

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Variants of KCNQ4 are one of the most common causes of dominantly inherited nonsyndromic hearing loss. We investigated a consanguineous family in which two individuals had prelignual hearing loss, apparently inherited in a recessive mode. Whole-exome sequencing analyses demonstrated genetic heterogeneity as variants in two different genes segregated with the phenotype in two branches of the family. Members in one branch were homozygous for a pathogenic variant of TMC1. The other two affected individuals were homozygous for a missense pathogenic variant in KCNQ4 c.872C>T; p.(Pro291Leu). These two individuals had prelingual, progressive moderate to severe hearing loss, while a heterozygous carrier had late onset mild hearing loss. Our work demonstrates that p.Pro291L variant is semi-dominantly inherited. This is the first report of semi-dominance of a KCNQ4 variant.

AB - Variants of KCNQ4 are one of the most common causes of dominantly inherited nonsyndromic hearing loss. We investigated a consanguineous family in which two individuals had prelignual hearing loss, apparently inherited in a recessive mode. Whole-exome sequencing analyses demonstrated genetic heterogeneity as variants in two different genes segregated with the phenotype in two branches of the family. Members in one branch were homozygous for a pathogenic variant of TMC1. The other two affected individuals were homozygous for a missense pathogenic variant in KCNQ4 c.872C>T; p.(Pro291Leu). These two individuals had prelingual, progressive moderate to severe hearing loss, while a heterozygous carrier had late onset mild hearing loss. Our work demonstrates that p.Pro291L variant is semi-dominantly inherited. This is the first report of semi-dominance of a KCNQ4 variant.

KW - ADNSHL

KW - ARNSHL

KW - Baylor-Hopkins Center for Mendelian Genomics

KW - BHCMG

KW - Deafness

KW - DFNA2A

KW - Hearing loss

KW - KCNQ4

KW - Pakistan

KW - WES

KW - Whole exome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85064952545&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064952545&partnerID=8YFLogxK

U2 - 10.1016/j.gene.2019.04.064

DO - 10.1016/j.gene.2019.04.064

M3 - Article

C2 - 31028865

AN - SCOPUS:85064952545

VL - 705

SP - 109

EP - 112

JO - Gene

JF - Gene

SN - 0378-1119

ER -