BACKGROUND: Connexin 26 (GJB2) mutations are associated with various types of hearing loss, either without associated symptoms or with skin disease, constituting a form of syndromic hearing loss. These mutations can lead to deafness in either a recessive or a dominant autosomal form of inheritance. METHODS: Ascertainment of a Jewish Ashkenazi family with nonsyndromic hearing loss led to the construction of a pedigree for a four-generation family, with hearing loss detected in three successive generations. The entire coding region of the GJB2 gene was amplified and sequenced by Sanger sequencing. RESULTS: Audiological analysis revealed that the age of onset and severity of hearing loss were earlier and more severe, respectively, in each successive generation of an Ashkenazi Jewish family. A mutation, c.224G>A, leading to missense p.Arg75Gln was detected only in the affected members of the family. CONCLUSIONS: The entire coding region of GJB2 should be checked in hearing-impaired patients by Sanger sequencing, rather than examination only of the two most prevalent mutations, regardless of mode of inheritance or ethnicity. Furthermore, predictions regarding phenotype based on genotype can be difficult to make due to clinical variability in multigenerational families, as demonstrated in the family presented in this study.
BACKGROUND:Connexin 26 (GJB2) mutations are associated with various types of hearing loss, either without associated symptoms or with skin disease, constituting a form of syndromic hearing loss. These mutations can lead to deafness in either a recessive or a dominant autosomal form of inheritance. METHODS: Ascertainment of a Jewish Ashkenazi family with nonsyndromic hearing loss led to the construction of a pedigree for a four-generation family, with hearing loss detected in three successive generations. The entire coding region of the GJB2 gene was amplified and sequenced by Sanger sequencing. RESULTS: Audiological analysis revealed that the age of onset and severity of hearing loss were earlier and more severe, respectively, in each successive generation of an Ashkenazi Jewish family. A mutation, c.224G>A, leading to missense p.Arg75Gln was detected only in the affected members of the family. CONCLUSIONS: The entire coding region of GJB2 should be checked in hearing-impairedpatients by Sanger sequencing, rather than examination only of the two most prevalent mutations, regardless of mode of inheritance or ethnicity. Furthermore, predictions regarding phenotype based on genotype can be difficult to make due to clinical variability in multigenerational families, as demonstrated in the family presented in this study.
Authors: D P Kelsell; J Dunlop; H P Stevens; N J Lench; J N Liang; G Parry; R F Mueller; I M Leigh Journal: Nature Date: 1997-05-01 Impact factor: 49.962
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Authors: Rikkert L Snoeckx; Patrick L M Huygen; Delphine Feldmann; Sandrine Marlin; Françoise Denoyelle; Jaroslaw Waligora; Malgorzata Mueller-Malesinska; Agneszka Pollak; Rafal Ploski; Alessandra Murgia; Eva Orzan; Pierangela Castorina; Umberto Ambrosetti; Ewa Nowakowska-Szyrwinska; Jerzy Bal; Wojciech Wiszniewski; Andreas R Janecke; Doris Nekahm-Heis; Pavel Seeman; Olga Bendova; Margaret A Kenna; Anna Frangulov; Heidi L Rehm; Mustafa Tekin; Armagan Incesulu; Hans-Henrik M Dahl; Desirée du Sart; Lucy Jenkins; Deirdre Lucas; Maria Bitner-Glindzicz; Karen B Avraham; Zippora Brownstein; Ignacio del Castillo; Felipe Moreno; Nikolaus Blin; Markus Pfister; Istvan Sziklai; Timea Toth; Philip M Kelley; Edward S Cohn; Lionel Van Maldergem; Pascale Hilbert; Anne-Françoise Roux; Michel Mondain; Lies H Hoefsloot; Cor W R J Cremers; Tuija Löppönen; Heikki Löppönen; Agnete Parving; Karen Gronskov; Iris Schrijver; Joseph Roberson; Francesca Gualandi; Alessandro Martini; Geneviéve Lina-Granade; Nathalie Pallares-Ruiz; Céu Correia; Graça Fialho; Kim Cryns; Nele Hilgert; Paul Van de Heyning; Carla J Nishimura; Richard J H Smith; Guy Van Camp Journal: Am J Hum Genet Date: 2005-10-19 Impact factor: 11.025
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