GJA1 mutations, variants, and connexin 43 dysfunction as it relates to the oculodentodigital dysplasia phenotype
| Autor: | Ethylin Wang Jabs, Barbara A. Karczeski, Lionel Van Maldergem, Joann Bodurtha, Sascha Vermeer, Martin B. Delatycki, William A. Paznekas, R. Brian Lowry, Simeon A. Boyadjiev, Faivre Laurence, Pasi A. Koivisto |
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| Rok vydání: | 2009 |
| Předmět: |
Genetics
Mutation Polymorphism Genetic Ataxia Hearing loss Molecular Sequence Data Connexin Biology Oculodentodigital dysplasia medicine.disease medicine.disease_cause Phenotype Genomic disorders and inherited multi-system disorders [IGMD 3] Hallermann–Streiff syndrome Palmoplantar keratoderma Connexin 43 medicine Humans Abnormalities Multiple Amino Acid Sequence medicine.symptom Genetics (clinical) |
| Zdroj: | Human Mutation, 30, 5, pp. 724-33 Human Mutation, 30, 724-33 |
| ISSN: | 1059-7794 |
| Popis: | Contains fulltext : 80660.pdf (Publisher’s version ) (Closed access) The predominantly autosomal dominant disorder, oculodentodigital dysplasia (ODDD) has high penetrance with intra- and interfamilial phenotypic variability. Abnormalities observed in ODDD affect the eye, dentition, and digits of the hands and feet. Patients present with a characteristic facial appearance, narrow nose, and hypoplastic alae nasi. Neurological problems, including dysarthria, neurogenic bladder disturbances, spastic paraparesis, ataxia, anterior tibial muscle weakness, and seizures, are known to occur as well as conductive hearing loss, cardiac defects, and anomalies of the skin, hair, and nails. In 2003, our analysis of 17 ODDD families revealed that each had a different mutation within the human gap junction alpha 1 (GJA1) gene which encodes the protein connexin 43 (Cx43). Since then at least 17 publications have identified an additional 26 GJA1 mutations and in this study, we present 28 new cases with 18 novel GJA1 mutations. We include tables summarizing the 62 known GJA1 nucleotide changes leading to Cx43 protein alterations and the phenotypic information available on 177 affected individuals from 54 genotyped families. Mutations resulting in ODDD occur in each of the nine domains of the Cx43 protein, and we review our functional experiments and those in the literature, examining the effects of 13 different Cx43 mutations upon gap junction activity. |
| Databáze: | OpenAIRE |
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