GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort of hearing-impaired patients.

Sandrine Marlin, Delphine Feldmann, Hélène Blons, Natalie Loundon, Isabelle Rouillon, Sébastien Albert, Pierre Chauvin, Eréa-Noël Garabédian, Rémy Couderc, Sylvie Odent, Alain Joannard, Sébastien Schmerber, Bruno Delobel, Jacques Leman, Hubert Journel, Hélène Catros, Cédric Lemarechal, Hélène Dollfus, Marie-Madeleine Eliot, Jean-Louis Delaunoy, Albert David, Catherine Calais, Valérie Drouin-Garraud, Marie-Françoise Obstoy, Cyril Goizet, Françoise Duriez, Florence Fellmann, Jocelyne Hélias, Jacqueline Vigneron, Bettina Montaut, Dominique Matin-Coignard, Laurence Faivre, Clarisse Baumann, Patricia Lewin, Christine Petit, Françoise Denoyelle
Arch Otolaryngol Head Neck Surg. 2005-06-01; 131(6): 481
DOI: 10.1001/archotol.131.6.481


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1. Arch Otolaryngol Head Neck Surg. 2005 Jun;131(6):481-7.

GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort
of hearing-impaired patients.

Marlin S(1), Feldmann D, Blons H, Loundon N, Rouillon I, Albert S, Chauvin P,
Garabédian EN, Couderc R, Odent S, Joannard A, Schmerber S, Delobel B, Leman J,
Journel H, Catros H, Lemarechal C, Dollfus H, Eliot MM, Delaunoy JL, David A,
Calais C, Drouin-Garraud V, Obstoy MF, Goizet C, Duriez F, Fellmann F, Hélias J,
Vigneron J, Montaut B, Matin-Coignard D, Faivre L, Baumann C, Lewin P, Petit C,
Denoyelle F.

Author information:
(1)Unité de Génétique Médicale, INSERM U587, Hôpital d’Enfants Armand-Trousseau,
AP-HP, Université Paris VI, Paris, France.

OBJECTIVES: To analyze the clinical features of hearing impairment and to search
for correlations with the genotype in patients with DFNB1.
DESIGN: Case series.
SETTING: Collaborative study in referral centers, institutional practice.
Patients A total of 256 hearing-impaired patients selected on the basis of the
presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation
with the GJB6 deletion (GJB6-D13S1830)del.
MAIN OUTCOME MEASURES: The prevalence of GJB2 mutations and the GJB6 deletion and
audiometric phenotypes related to the most frequent genotypes.
RESULTS: Twenty-nine different GJB2 mutations were identified. Allelic frequency
of 35delG was 69%, and the other common mutations, 313del14, E47X, Q57X, and
L90P, accounted for 2.6% to 2.9% of the variants. Concerning GJB6,
(GJB6-D13S1830)del accounted for 5% of all mutated alleles and was observed in 25
of 93 compound heterozygous patients. Three novel GJB2 mutations, 355del9, V95M,
and 573delCA, were identified. Hearing impairment was frequently less severe in
compound heterozygotes 35delG/L90P and 35delG/N206S than in 35delG homozygotes.
Moderate or mild hearing impairment was more frequent in patients with 1 or 2
noninactivating mutations than in patients with 2 inactivating mutations. Of 93
patients, hearing loss was stable in 73, progressive in 21, and fluctuant in 2.
Progressive hearing loss was more frequent in patients with 1 or 2
noninactivating mutations than in those with 2 inactivating mutations. In 49
families, hearing loss was compared between siblings with similar genotypes, and
variability in terms of severity was found in 18 families (37%).
CONCLUSION: Genotype may affect deafness severity, but environmental and other
genetic factors may also modulate the severity and evolution of GJB2-GJB6
deafness.

DOI: 10.1001/archotol.131.6.481
PMID: 15967879 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus