title: Molecular heterogeneity in two families with auditory pigmentary syndromes: the role of neuroimaging and genetic analysis in deafness.
abstract: We report two cases in which the probands presented with deafness and a family history of a dominantly inherited auditory pigmentary syndrome, yet the cause of deafness in each proband was not associated with the pigmentary abnormalities but was a result of mutations in SLC26A4, the gene mutated in Pendred's syndrome. The first case is a young woman with congenital sensorineural hearing loss and a family history of piebaldism. Despite showing no pigmentary abnormalities, the proband was found to harbor the same KIT mutation as her relatives affected by piebaldism, as well as two mutations in the SLC26A4 gene. In the second case, 2-year-old identical twin boys born to deaf parents presented with congenital sensorineural deafness and an extensive maternal family history of Waardenburg's syndrome type I (WSI). Their father had recessively inherited deafness associated with dilated vestibular aqueducts and a clinical diagnosis of Pendred's syndrome was made in him, which was confirmed molecularly. As the twin boys did not have features of WSI, both the mother and children were tested for mutations in SLC26A4 which showed the mother to be a carrier of a single mutation and both boys to be compound heterozygotes, illustrating pseudodominant inheritance of the condition.
authors.affiliation: Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Shears
authors.forename: H
authors.initials: H
authors.lastname: Conlon
authors.forename: T
authors.initials: T
authors.lastname: Murakami
authors.forename: K
authors.initials: K
authors.lastname: Fukai
authors.forename: R
authors.initials: R
authors.lastname: Alles
authors.forename: R
authors.initials: R
authors.lastname: Trembath
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
mesh_terms: D000328:Adult; D002675:Child, Preschool; D004200:Diseases in Twins; D004423:Ear / Q000473:pathology; D005260:Female; D018740:Genetic Heterogeneity; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D015513:Oncogene Proteins / Q000235:genetics; D016116:Piebaldism / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D050486:Serotonin Plasma Membrane Transport Proteins; D013577:Syndrome; D014057:Tomography, X-Ray Computed; D014849:Waardenburg Syndrome / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D019009:Proto-Oncogene Proteins c-kit