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Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling
S Marlin1, E N Garabédian, G Roger
1Service d'ORL Pédiatrique et de Chirurgie Cervicofaciale, Hôpital d'Enfants Armand-Trousseau, and Université Paris VI, Paris CEDEX 05, France.
Insights
Genetic counseling for deaf children with connexin 26 gene (CX26) mutations is challenging in nearly one-third of cases. Accurate molecular diagnosis requires collaboration between geneticists and otolaryngologists.
Area of Science:
- Genetics
- Otolaryngology
- Pediatrics
Background:
- Congenital deafness is a significant health concern in children.
- Connexin 26 gene (CX26 or GJB2) mutations are a common cause of hereditary non-syndromic sensorineural hearing loss.
- Genetic counseling plays a crucial role in understanding inheritance patterns and implications for families.
Purpose of the Study:
- To evaluate the challenges and difficulties encountered during genetic counseling for deaf children with CX26 mutations.
- To identify specific genetic factors contributing to diagnostic complexity.
Main Methods:
- Prospective study involving 96 unrelated deaf children with confirmed CX26 mutations.
- Children were recruited from a tertiary referral center for genetic counseling.
- Genetic analysis focused on identifying mutation types and inheritance patterns.
Main Results:
- In 63 children, deafness was attributed to DFNB1 autosomal recessive inheritance, with 47 homozygous for the 35delG mutation.
- Genetic counseling was difficult in 33 out of 96 children.
- Difficulties arose from single mutations, novel or debated missense mutations, or complex genotypes involving both recessive and dominant mutations.
Conclusions:
- Interpreting molecular diagnostic results for CX26 gene mutations is challenging in approximately one-third of cases.
- Close collaboration between geneticists specializing in deafness and otolaryngologists is essential for high-quality genetic advice.
- Addressing complex genetic findings improves the standard of care for deaf children and their families.
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.