Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in pendred syndrome

Núria López-Bigas, Raquel Rabionet, Rafael De Cid, Nancy Govea, Paolo Gasparini, Leopoldo Zelante, Maria Lourdes Arbonés, Xavier P. Estivill

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, and encodes a chloride-iodide transport protein. We performed mutation analysis of individual exons of the PDS gene in one Spanish family that shows intrafamilial variability of the deafness phenotype (two patients with profound and one with moderate-severe deafness). We identified a new splice-site mutation affecting intron 4 of the PDS gene, at nucleotide position 639+7. RNA analysis from lymphocytes of the affected patients showed that mutation 639 + 7A→G generates a new donor splice site, leading to an mRNA with an insertion of six nucleotides from intron 4 of PDS. Since the newly created donor splice site is likely to compete with the normal one, variations of the levels of normal and aberrant transcripts of the PDS gene in the cochlea may explain the variability in the deafness presentation.

Original languageEnglish
Pages (from-to)520-526
Number of pages7
JournalHuman Mutation
Volume14
Issue number6
DOIs
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Deafness
RNA Splice Sites
Mutation
Cochlea
Introns
Genes
Nucleotides
Sensorineural Hearing Loss
Goiter
Iodides
Chlorides
Exons
Carrier Proteins
Thyroid Gland
Chromosomes
Lymphocytes
RNA
Phenotype
Messenger RNA
Pendred syndrome

Keywords

  • Deafness
  • Hearing loss
  • PDS
  • Pendred syndrome
  • Pendrin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in pendred syndrome. / López-Bigas, Núria; Rabionet, Raquel; De Cid, Rafael; Govea, Nancy; Gasparini, Paolo; Zelante, Leopoldo; Arbonés, Maria Lourdes; Estivill, Xavier P.

In: Human Mutation, Vol. 14, No. 6, 1999, p. 520-526.

Research output: Contribution to journalArticle

López-Bigas, Núria ; Rabionet, Raquel ; De Cid, Rafael ; Govea, Nancy ; Gasparini, Paolo ; Zelante, Leopoldo ; Arbonés, Maria Lourdes ; Estivill, Xavier P. / Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in pendred syndrome. In: Human Mutation. 1999 ; Vol. 14, No. 6. pp. 520-526.
@article{c068025cad924a3d95feae6177c4e63f,
title = "Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in pendred syndrome",
abstract = "Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10{\%} of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, and encodes a chloride-iodide transport protein. We performed mutation analysis of individual exons of the PDS gene in one Spanish family that shows intrafamilial variability of the deafness phenotype (two patients with profound and one with moderate-severe deafness). We identified a new splice-site mutation affecting intron 4 of the PDS gene, at nucleotide position 639+7. RNA analysis from lymphocytes of the affected patients showed that mutation 639 + 7A→G generates a new donor splice site, leading to an mRNA with an insertion of six nucleotides from intron 4 of PDS. Since the newly created donor splice site is likely to compete with the normal one, variations of the levels of normal and aberrant transcripts of the PDS gene in the cochlea may explain the variability in the deafness presentation.",
keywords = "Deafness, Hearing loss, PDS, Pendred syndrome, Pendrin",
author = "N{\'u}ria L{\'o}pez-Bigas and Raquel Rabionet and {De Cid}, Rafael and Nancy Govea and Paolo Gasparini and Leopoldo Zelante and Arbon{\'e}s, {Maria Lourdes} and Estivill, {Xavier P.}",
year = "1999",
doi = "10.1002/(SICI)1098-1004(199912)14:6<520::AID-HUMU11>3.0.CO;2-K",
language = "English",
volume = "14",
pages = "520--526",
journal = "Human Mutation",
issn = "1059-7794",
publisher = "Wiley-Liss Inc.",
number = "6",

}

TY - JOUR

T1 - Splice-site mutation in the PDS gene may result in intrafamilial variability for deafness in pendred syndrome

AU - López-Bigas, Núria

AU - Rabionet, Raquel

AU - De Cid, Rafael

AU - Govea, Nancy

AU - Gasparini, Paolo

AU - Zelante, Leopoldo

AU - Arbonés, Maria Lourdes

AU - Estivill, Xavier P.

PY - 1999

Y1 - 1999

N2 - Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, and encodes a chloride-iodide transport protein. We performed mutation analysis of individual exons of the PDS gene in one Spanish family that shows intrafamilial variability of the deafness phenotype (two patients with profound and one with moderate-severe deafness). We identified a new splice-site mutation affecting intron 4 of the PDS gene, at nucleotide position 639+7. RNA analysis from lymphocytes of the affected patients showed that mutation 639 + 7A→G generates a new donor splice site, leading to an mRNA with an insertion of six nucleotides from intron 4 of PDS. Since the newly created donor splice site is likely to compete with the normal one, variations of the levels of normal and aberrant transcripts of the PDS gene in the cochlea may explain the variability in the deafness presentation.

AB - Pendred syndrome is a recessive inherited disorder that consists of developmental abnormalities of the cochlea, sensorineural hearing loss, and diffuse thyroid enlargement (goiter). This disorder may account for up to 10% of cases of hereditary deafness. The disease gene (PDS) has been mapped to chromosome 7q22-q31, and encodes a chloride-iodide transport protein. We performed mutation analysis of individual exons of the PDS gene in one Spanish family that shows intrafamilial variability of the deafness phenotype (two patients with profound and one with moderate-severe deafness). We identified a new splice-site mutation affecting intron 4 of the PDS gene, at nucleotide position 639+7. RNA analysis from lymphocytes of the affected patients showed that mutation 639 + 7A→G generates a new donor splice site, leading to an mRNA with an insertion of six nucleotides from intron 4 of PDS. Since the newly created donor splice site is likely to compete with the normal one, variations of the levels of normal and aberrant transcripts of the PDS gene in the cochlea may explain the variability in the deafness presentation.

KW - Deafness

KW - Hearing loss

KW - PDS

KW - Pendred syndrome

KW - Pendrin

UR - http://www.scopus.com/inward/record.url?scp=0344577853&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344577853&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-1004(199912)14:6<520::AID-HUMU11>3.0.CO;2-K

DO - 10.1002/(SICI)1098-1004(199912)14:6<520::AID-HUMU11>3.0.CO;2-K

M3 - Article

C2 - 10571950

AN - SCOPUS:0344577853

VL - 14

SP - 520

EP - 526

JO - Human Mutation

JF - Human Mutation

SN - 1059-7794

IS - 6

ER -