 |
|
Connexin 26 Gene Mutations in Congenitally Deaf Children
Pitfalls for Genetic Counseling
Sandrine Marlin, MD, PhD;
Éréa-Noël Garabédian, MD;
Gilles Roger, MD;
Lucien Moatti, MD;
Nicole Matha, MD;
Patricia Lewin, MD;
Christine Petit, MD, PhD;
Françoise Denoyelle, MD, PhD
Arch Otolaryngol Head Neck Surg. 2001;127:927-933.
Objective To evaluate difficulties encountered in genetic counseling in deaf children
carrying connexin 26 gene (CX26 or GJB2) mutations.
Design Prospective study.
Setting Outpatients, tertiary referral center.
Patients Ninety-six unrelated deaf children in whom CX26 mutations
had been detected consecutively. Children were recruited to a center for genetic
counseling for deaf children, and all had congenital deafness, sporadic or
familial.
Results In 63 children, deafness was clearly a DFNB1 form with autosomal recessive
inheritance: 47 of the 63 were homozygous for the most frequent mutation,
the deletion of G at position 35 (35delG); 16 of 63 carried on
both alleles of CX26 frameshift or stop mutations, or missense
mutations affecting a critical region of the gene. In 33 of 96 children, genetic
counseling was difficult: 21 of 33 had a single mutation detected, 11 of 33
had new missense mutations or mutations whose pathogenicity remains debated
in the literature, and 1 of 33 had a genotype with both a recessive mutation
(35delG) and a mutation acting as a dominant mutation.
Conclusions Interpretation of results for the molecular diagnosis of mutations in
the connexin 26 gene is difficult in almost one third of cases. Close collaboration
between geneticists familiar with deafness and otolaryngologists is essential
to provide a high standard of genetic advice.
From the Service d'ORL Pédiatrique et de Chirurgie Cervicofaciale,
Hôpital d'Enfants Armand-Trousseau, and Université Paris VI,
Paris, France (Drs Marlin, Garabédian, Roger, Moatti, Matha, and Denoyelle);
Laboratoire Pasteur-Cerba, Cergy-Pontoise, France (Dr Lewin); and Unité
de Génétique des Déficits Sensoriels, Institut Pasteur,
Paris (Dr Petit).
RELATED ARTICLES
Archives of Otolaryngology–Head & Neck Surgery Reader's Choice: Continuing Medical Education
Arch Otolaryngol Head Neck Surg. 2001;127(8):1011-1012.
FULL TEXT
Pediatric Otolaryngologists' Knowledge and Understanding of Genetic Testing for Deafness
Nathaniel H. Robin, Christin Dietz, James E. Arnold, and Richard J. H. Smith
Arch Otolaryngol Head Neck Surg. 2001;127(8):937-940.
ABSTRACT
| FULL TEXT
Mutation Screening for Deafness: More Than Simply Another Diagnostic Test
Richard J. H. Smith
Arch Otolaryngol Head Neck Surg. 2001;127(8):941-942.
EXTRACT
| FULL TEXT
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
The Structural Context of Disease-causing Mutations in Gap Junctions
Fleishman et al.
J. Biol. Chem. 2006;281:28958-28963.
ABSTRACT
| FULL TEXT
Pathogenetic role of the deafness-related M34T mutation of Cx26
Bicego et al.
Hum Mol Genet 2006;15:2569-2587.
ABSTRACT
| FULL TEXT
GJB2 and GJB6 Mutations: Genotypic and Phenotypic Correlations in a Large Cohort of Hearing-Impaired Patients
Marlin et al.
Arch Otolaryngol Head Neck Surg 2005;131:481-487.
ABSTRACT
| FULL TEXT
A genotype-phenotype correlation for GJB2 (connexin 26) deafness
Cryns et al.
J. Med. Genet. 2004;41:147-154.
ABSTRACT
| FULL TEXT
Hereditary deafness and phenotyping in humans
Bitner-Glindzicz
Br Med Bull 2002;63:73-94.
ABSTRACT
| FULL TEXT
Auditory Function and the M34T Allele of Connexin 26
Griffith and Friedman
Arch Otolaryngol Head Neck Surg 2002;128:94-94.
FULL TEXT
Quo Vadis Otologica?
Wiet et al.
Arch Otolaryngol Head Neck Surg 2001;127:1431-1432.
FULL TEXT
Mutation Screening for Deafness: More Than Simply Another Diagnostic Test
Smith
Arch Otolaryngol Head Neck Surg 2001;127:941-942.
FULL TEXT
|
