The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major non-collagenous components of the tectorial membrane. Recently, the gene encoding mouse alpha-tectorin (Tecta) was mapped to a region of mouse chromosome 9, which shows evolutionary conservation with human chromosome 11q (ref. 3), where linkage was found in two families, one Belgian (DFNA12; ref. 4) and the other, Austrian (DFNA8; unpublished data), with autosomal dominant non-syndromic hearing impairment. We determined the complete sequence and the intron-exon structure of the human TECTA gene. In both families, mutation analysis revealed missense mutations which replace conserved amino-acid residues within the zona pellucida domain of TECTA. These findings indicate that mutations in TECTA are responsible for hearing impairment in these families, and implicate a new type of protein in the pathogenesis of hearing impairment.
Branchiootorenal (BOR) syndrome is a variable, autosomal-dominant disorder of the first and second embryonic branchial arches, kidneys, and urinary tract. We describe the phenotype in 45 individuals, highlighting differences and similarities reported in other studies. Characteristic temporal bone findings include cochlear hypoplasia (4/5 of normal size with only 2 turns), dilation of the vestibular aqueduct, bulbous internal auditory canals, deep posterior fossae, and acutely-angled promontories.
Autosomal recessive non-syndromic hearing loss (ARNSHL) is the most common form of prelingual inherited hearing impairment. A small consanguineous family with this disorder was ascertained through the Institute of Basic Medical Sciences in Madras, India. Conditions such as rubella, prematurity, drug use during pregnancy, perinatal trauma, and meningitis were eliminated by history. Audiometry was performed to confirm severe-to-profound hearing impairment in affected persons. After excluding linkage to known DFNB genes, two genomic DNA pools, one from the affected persons and the other from their non-affected siblings and the parents, were used to screen 165 polymorphic markers evenly spaced across the autosomal human genome. Two regions showing homozygosity-by-descent in the affected siblings were identified on chromosomes 3q21.3-q25.2 and 19p13.3-p13.1, identifying one (or possibly both) as the site of a novel ARNSHL gene.
Late-onset non-syndromic hearing impairment is the most common type of neurological dysfunction in the elderly. It can be either acquired or inherited, although the relative impact of heredity on this type of loss is not known. To date, nine different genes have been localized, but none has been cloned. Using an extended American family in which a gene for autosomal dominant late-onset non-syndromic hearing impairment is segregating, we have identified a new locus, DFNA10, on chromosome 6.
Autosomal recessive nonsyndromic sensorineural deafness segregating in a large consanguineous Indian family was mapped to chromosome 11p14 -p15.1 defining a new locus, DFNB18. A maximum lod score of 4.4 at ⍜ ؍ 0 was obtained for the polymorphic microsatellite marker D11S1888. Haplotype analysis localizes this gene between markers D11S1307 and D11S2368, which is approximately 1.6 cM and encompasses the region of Usher syndrome type 1C (USH1C). We postulate that DFNB18 and USH1C are allelic variants of the same gene.
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