USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23 - PubMed (original) (raw)

USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23

Z M Ahmed et al. Clin Genet. 2009 Jan.

Abstract

Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Chromosome 15 haplotypes in USH1H families PKDF125 and PKDF117. Filled symbols represent deaf individuals. The USH1H-linked haplotype is color-coded. The STR markers and genetic map positions in centiMorgans (cM) are taken from the Marshfield human genetic map. Haplotype analysis of PKDF125 shows a linkage region of 4.92 cM delimited by markers D15S988 (66.90 cM) and D15S967 (71.82 cM). Affected individuals III:1 and III:2 provided both proximal and distal meiotic breakpoints at marker D15S988 (66.90 cM) and D15S967 (71.82 cM), respectively. In family PKDF117 affected individual VI:1 provided the proximal meiotic breakpoint at marker D15S988 (66.90 cM). The distal breakpoint at marker D15S1005 (75.27 cM) was provided by normal hearing individual V:13. Also given are the maximum two-point lod scores for each STR linked to USH1H.

Fig. 2

Fig. 2

USH1H linkage intervals in families PKDF125 and PKDF117 on human chromosome 15q22-23. STR markers are represented by filled circles. The sex averaged recombination positions in cM and physical map positions in Mb (not drawn to scale) are indicated for STR markers (Center for Medical Genetics, Marshfield Medical Research Foundation, (

http://research.marshfieldclinic.org/genetics

). Candidate genes in the USH1H interval were identified from the UCSC Human Genome Browser March 2006 assembly (

http://genome.ucsc.edu/

).

References

    1. Smith RJ, Berlin CI, Hejtmancik JF, et al. Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium. Am J Med Genet. 1994;50:32–38. - PubMed
    1. Boughman JA, Vernon M, Shaver KA. Usher syndrome: definition and estimate of prevalence from two high-risk populations. J Chronic Dis. 1983;36:595–603. - PubMed
    1. Brownstein Z, Ben-Yosef T, Dagan O, et al. The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa. Pediatr Res. 2004;55:995–1000. - PubMed
    1. Vernon M. Usher’s syndrome--deafness and progressive blindness. Clinical cases, prevention, theory and literature survey. J Chronic Dis. 1969;22:133–151. - PubMed
    1. Ahmed ZM, Riazuddin S, Bernstein SL, et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet. 2001;69:25–34. - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources