Identification of a novel locus for a USH3 like syndrome combined with congenital cataract

• Published in: Clinical genetics 2010-10, Vol.78 (4), p.388-397
• Main Authors: Dad, S, Østergaard, E, Thykjær, T, Albrectsen, A, Ravn, K, Rosenberg, T, Møller, LB
• Format: Article
• Language: English
• Subjects: 15q22-23; Base Sequence; Biological and medical sciences; Blindness; Cataract - congenital; Cataract - embryology; Cataract - genetics; Cataracts; chromosome 15; Chromosome Mapping; Chromosomes, Human, Pair 15 - genetics; congenital cataract; Congenital diseases; Consanguinity; Deafness; Denmark; DNA Mutational Analysis; Female; Fundamental and applied biological sciences. Psychology; Gene mapping; General aspects. Genetic counseling; Genetic disorders; Genetic Linkage; Genetic Loci; Genetics of eukaryotes. Biological and molecular evolution; Genotype; Genotype & phenotype; Hearing loss; Humans; Lod Score; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Netherlands; Pedigree; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Retinitis pigmentosa; Retinitis Pigmentosa - genetics; Sequence Analysis, DNA; USH3 locus; usher syndrome; Usher Syndromes - genetics; Vestibular system
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2010.01393.x

Dad S, Østergaard E, Thykjær T, Albrectsen A, Ravn K, Rosenberg T, Møller LB. Identification of a novel locus for a USH3 like syndrome combined with congenital cataract. Usher syndrome (USH) is the most common genetic disease that causes both deafness and blindness. USH is divided into three types, USH1, USH2 and USH3, depending on the age of onset, the course of the disease, and on the degree of vestibular dysfunction. By homozygosity mapping of a consanguineous Danish family of Dutch descent, we have identified a novel locus for a rare USH3‐like syndrome. The affected family members have a unique association of retinitis pigmentosa, progressive hearing impairment, vestibular dysfunction, and congenital cataract. The phenotype is similar, but not identical to that of USH3 patients, as congenital cataract has not been reported for USH3. By homozygosity mapping, we identified a 7.3 Mb locus on chromosome 15q22.2‐23 with a maximum multipoint LOD score of 2.0. The locus partially overlaps with the USH1 locus, USH1H, a novel unnamed USH2 locus, and the non‐syndromic deafness locus DFNB48.