Three novel GJB2 (connexin 26) variants associated with autosomal dominant syndromic and nonsyndromic hearing loss
| Autor: | John C. Carey, Janice C. Palumbos, Colleen M. Carlston, Oliver H. Tam, David Viskochil, Heather J. Stalker, Desiree DeMille, Rong Mao, Roberto T. Zori, Albert H. Park |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proband Male Models Molecular Hearing loss Protein Conformation Inheritance Patterns Connexin Biology Deafness 03 medical and health sciences 0302 clinical medicine otorhinolaryngologic diseases Genetics medicine Humans Keratoderma Child Gene Genetics (clinical) Genetic Association Studies Genes Dominant Computational Biology Genetic Variation medicine.disease Phenotype Connexin 26 030104 developmental biology Tandem Repeat Sequences Child Preschool Leukonychia Sensorineural hearing loss Female medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | American journal of medical genetics. Part A. 176(4) |
| ISSN: | 1552-4833 |
| Popis: | Connexin 26 (Cx26), encoded by the GJB2 gene, is a key protein involved in the formation of gap junctions in epithelial organs including the inner ear and palmoplantar epidermis. Pathogenic variants in GJB2 are responsible for approximately 50% of inherited sensorineural deafness. The majority of these variants are associated with autosomal recessive inheritance; however, rare reports of dominantly co-segregating variants have been published. Since we began offering GJB2 testing in 2003, only about 2% of detected GJB2 variants from our laboratory have been classified as dominant. Here we report three novel dominant GJB2 variants (p.Thr55Ala, p.Gln57_Pro58delinsHisSer, and p.Trp44Gly); two associated with syndromic sensorineural hearing loss and one with nonsyndromic hearing loss. In the kindred with the p.Thr55Ala variant, the proband and his father present with only leukonychia as a cutaneous finding of their syndromic hearing loss. This phenotype has been previously documented in conjunction with palmoplantar hyperkeratosis, but isolated leukonychia is a novel finding likely associated with the unique threonine to alanine change at codon 55 (other variants at this codon have been reported in cases of nonsyndromic hearing loss). This report contributes to the short list of GJB2 variants associated with autosomal dominant hearing loss, highlights the variability of skin and nail findings associated with such cases, and illustrates the occurrence of both syndromic and nonsyndromic presentations with changes in the same gene. |
| Databáze: | OpenAIRE |
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