Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans

Leopolde Zelante, Paolo Gasparini, Xavier P. Estivill, Salvatore Melchionda, Leonardo D'Agruma, Nancy Govea, Monserrat Milá, Matteo Della Monica, Jaber Lutfi, Mordechai Shohat, Elaine Mansfield, Kathleen Delgrosso, Eric Rappaport, Saul Surrey, Paolo Fortina

Research output: Contribution to journalArticle

504 Citations (Scopus)

Abstract

Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for ~ 80% of cases in the Mediterranean area. Further analysis with additional markers now identifies several recombinants which narrow the canididate region to ~ 5 cM, encompassed by markers D13S141 and D13S232 and including several ESTs and candidate genes, including the connexin26 (GJB2) gene. Analysis of PCR products from our affected patients' DNA shows two frameshift mutations in the connexin26 gene. Deletion of a G within a stretch of six Gs at position 35 of the GJB2 cDNA (mutation 35delG) leads to premature chain termination and is present in 63% of NSRD chromosomes, demonstrating linkage to chromosome 13. Deletion of a T at position 167 of GJB2 (mutation 167delT), also resulting in premature chain termination, was detected in another patient. Four neutral sequence polymorphisms were also identified. These findings are in agreement with a recent study showing that mutations in the connexin26 gene are associated with genetic forms of deafness in three Pakistani families and that GJB2 is DFNB1. Connexin26 is a member of a large family of proteins involved in formation of gap junctions, which are involved in electrical synapses and the direct transfer of small molecules and ionic currents between neighboring cells. The identification of GJB2 as the DFNB1 gene should provide a better understanding of the biology of normal and abnormal hearing, help form the basis for diagnosis and may facilitate development of strategies for treatment of this common genetic disorder.

Original languageEnglish
Pages (from-to)1605-1609
Number of pages5
JournalHuman Molecular Genetics
Volume6
Issue number9
DOIs
Publication statusPublished - Sep 1997
Externally publishedYes

Fingerprint

Mutation
Chromosomes, Human, Pair 13
Genes
Electrical Synapses
Frameshift Mutation
Inborn Genetic Diseases
Gap Junctions
Expressed Sequence Tags
Deafness
Hearing Loss
Hearing
Complementary DNA
Chromosomes
Autosomal Recessive Deafness
Polymerase Chain Reaction
DNA
Proteins
Therapeutics

ASJC Scopus subject areas

  • Genetics

Cite this

Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. / Zelante, Leopolde; Gasparini, Paolo; Estivill, Xavier P.; Melchionda, Salvatore; D'Agruma, Leonardo; Govea, Nancy; Milá, Monserrat; Della Monica, Matteo; Lutfi, Jaber; Shohat, Mordechai; Mansfield, Elaine; Delgrosso, Kathleen; Rappaport, Eric; Surrey, Saul; Fortina, Paolo.

In: Human Molecular Genetics, Vol. 6, No. 9, 09.1997, p. 1605-1609.

Research output: Contribution to journalArticle

Zelante, L, Gasparini, P, Estivill, XP, Melchionda, S, D'Agruma, L, Govea, N, Milá, M, Della Monica, M, Lutfi, J, Shohat, M, Mansfield, E, Delgrosso, K, Rappaport, E, Surrey, S & Fortina, P 1997, 'Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans', Human Molecular Genetics, vol. 6, no. 9, pp. 1605-1609. https://doi.org/10.1093/hmg/6.9.1605
Zelante, Leopolde ; Gasparini, Paolo ; Estivill, Xavier P. ; Melchionda, Salvatore ; D'Agruma, Leonardo ; Govea, Nancy ; Milá, Monserrat ; Della Monica, Matteo ; Lutfi, Jaber ; Shohat, Mordechai ; Mansfield, Elaine ; Delgrosso, Kathleen ; Rappaport, Eric ; Surrey, Saul ; Fortina, Paolo. / Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. In: Human Molecular Genetics. 1997 ; Vol. 6, No. 9. pp. 1605-1609.
@article{87a4cc8d6b414c7abafd5cfa634aeab6,
title = "Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans",
abstract = "Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for ~ 80{\%} of cases in the Mediterranean area. Further analysis with additional markers now identifies several recombinants which narrow the canididate region to ~ 5 cM, encompassed by markers D13S141 and D13S232 and including several ESTs and candidate genes, including the connexin26 (GJB2) gene. Analysis of PCR products from our affected patients' DNA shows two frameshift mutations in the connexin26 gene. Deletion of a G within a stretch of six Gs at position 35 of the GJB2 cDNA (mutation 35delG) leads to premature chain termination and is present in 63{\%} of NSRD chromosomes, demonstrating linkage to chromosome 13. Deletion of a T at position 167 of GJB2 (mutation 167delT), also resulting in premature chain termination, was detected in another patient. Four neutral sequence polymorphisms were also identified. These findings are in agreement with a recent study showing that mutations in the connexin26 gene are associated with genetic forms of deafness in three Pakistani families and that GJB2 is DFNB1. Connexin26 is a member of a large family of proteins involved in formation of gap junctions, which are involved in electrical synapses and the direct transfer of small molecules and ionic currents between neighboring cells. The identification of GJB2 as the DFNB1 gene should provide a better understanding of the biology of normal and abnormal hearing, help form the basis for diagnosis and may facilitate development of strategies for treatment of this common genetic disorder.",
author = "Leopolde Zelante and Paolo Gasparini and Estivill, {Xavier P.} and Salvatore Melchionda and Leonardo D'Agruma and Nancy Govea and Monserrat Mil{\'a} and {Della Monica}, Matteo and Jaber Lutfi and Mordechai Shohat and Elaine Mansfield and Kathleen Delgrosso and Eric Rappaport and Saul Surrey and Paolo Fortina",
year = "1997",
month = "9",
doi = "10.1093/hmg/6.9.1605",
language = "English",
volume = "6",
pages = "1605--1609",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans

AU - Zelante, Leopolde

AU - Gasparini, Paolo

AU - Estivill, Xavier P.

AU - Melchionda, Salvatore

AU - D'Agruma, Leonardo

AU - Govea, Nancy

AU - Milá, Monserrat

AU - Della Monica, Matteo

AU - Lutfi, Jaber

AU - Shohat, Mordechai

AU - Mansfield, Elaine

AU - Delgrosso, Kathleen

AU - Rappaport, Eric

AU - Surrey, Saul

AU - Fortina, Paolo

PY - 1997/9

Y1 - 1997/9

N2 - Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for ~ 80% of cases in the Mediterranean area. Further analysis with additional markers now identifies several recombinants which narrow the canididate region to ~ 5 cM, encompassed by markers D13S141 and D13S232 and including several ESTs and candidate genes, including the connexin26 (GJB2) gene. Analysis of PCR products from our affected patients' DNA shows two frameshift mutations in the connexin26 gene. Deletion of a G within a stretch of six Gs at position 35 of the GJB2 cDNA (mutation 35delG) leads to premature chain termination and is present in 63% of NSRD chromosomes, demonstrating linkage to chromosome 13. Deletion of a T at position 167 of GJB2 (mutation 167delT), also resulting in premature chain termination, was detected in another patient. Four neutral sequence polymorphisms were also identified. These findings are in agreement with a recent study showing that mutations in the connexin26 gene are associated with genetic forms of deafness in three Pakistani families and that GJB2 is DFNB1. Connexin26 is a member of a large family of proteins involved in formation of gap junctions, which are involved in electrical synapses and the direct transfer of small molecules and ionic currents between neighboring cells. The identification of GJB2 as the DFNB1 gene should provide a better understanding of the biology of normal and abnormal hearing, help form the basis for diagnosis and may facilitate development of strategies for treatment of this common genetic disorder.

AB - Non-syndromic neurosensory autosomal recessive deafness (NSRD) is the most common form of genetic hearing loss. Previous studies defined at least 15 human NSRD loci. Recently we demonstrated that DFNB1, located on the long arm of chromosome 13, accounts for ~ 80% of cases in the Mediterranean area. Further analysis with additional markers now identifies several recombinants which narrow the canididate region to ~ 5 cM, encompassed by markers D13S141 and D13S232 and including several ESTs and candidate genes, including the connexin26 (GJB2) gene. Analysis of PCR products from our affected patients' DNA shows two frameshift mutations in the connexin26 gene. Deletion of a G within a stretch of six Gs at position 35 of the GJB2 cDNA (mutation 35delG) leads to premature chain termination and is present in 63% of NSRD chromosomes, demonstrating linkage to chromosome 13. Deletion of a T at position 167 of GJB2 (mutation 167delT), also resulting in premature chain termination, was detected in another patient. Four neutral sequence polymorphisms were also identified. These findings are in agreement with a recent study showing that mutations in the connexin26 gene are associated with genetic forms of deafness in three Pakistani families and that GJB2 is DFNB1. Connexin26 is a member of a large family of proteins involved in formation of gap junctions, which are involved in electrical synapses and the direct transfer of small molecules and ionic currents between neighboring cells. The identification of GJB2 as the DFNB1 gene should provide a better understanding of the biology of normal and abnormal hearing, help form the basis for diagnosis and may facilitate development of strategies for treatment of this common genetic disorder.

UR - http://www.scopus.com/inward/record.url?scp=9844245885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9844245885&partnerID=8YFLogxK

U2 - 10.1093/hmg/6.9.1605

DO - 10.1093/hmg/6.9.1605

M3 - Article

VL - 6

SP - 1605

EP - 1609

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

ER -