Further refinement of the Usher 2A locus at 1q41

• Published in: Journal of medical genetics Vol. 35; no. 9; pp. 773 - 774
• Main Authors: Bessant, D A, Payne, A M, Plant, C, Bird, A C, Bhattacharya, S S
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.09.1998; BMJ; BMJ Publishing Group LTD
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 1 - genetics; Consanguinity; Extracellular Matrix Proteins - genetics; Genetic Markers; Hearing Loss, Sensorineural - genetics; Humans; Male; Medical sciences; Molecular Sequence Data; Ophthalmology; Pedigree; Recombination, Genetic; Retinitis Pigmentosa - genetics; Retinopathies; Syndrome; Genetic mapping; Human; Retinopathy; Linkage; Family study; Pathogenesis; Nutrition disorder; Chromosome A1; Genetic determinism; Genetic disease; Eye disease; Usher syndrome; ENT disease
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.35.9.773

Usher syndrome (USH) is characterised by congenital sensorineural hearing loss and progressive pigmentary retinopathy. All three subtypes (USH1, USH2, and USH3) are inherited as recessive traits. People with Usher type 2 (USH2) have normal vestibular responses and moderate to severe hearing loss. These syndromes have been found to be genetically heterogeneous, with a single locus for USH2 at 1q41 (USH2A), six loci for USH1, and one for USH3. Some USH2 families have been excluded from the 1q41 locus suggesting that a second, as yet unidentified, locus (USH2B) must exist. Linkage studies suggest that around 90% of USH2 families are USH2A. Four USH2 families were analysed for linkage to markers flanking the USH2A locus. In one of these families a recombination event was observed in an affected subject which excludes the USH2A gene from proximal to the marker AFM143XF10 and defines this as the new centromeric flanking marker for the USH2A locus. A further recombination event in another patient from this family confirmed AFM144XF2 as the telomeric flanking marker. The interval between these polymorphic markers is estimated to be 400 kb. This region is completely contained in each of three YACs from the CEPH library: 867g9, 919h3, and 848b9. This refinement more than halves the critical genetic interval and will greatly facilitate positional cloning of the USH2A gene.