A common ancestral origin of the frequent and widespread 2299delG USH2A mutation - PubMed (original) (raw)

A common ancestral origin of the frequent and widespread 2299delG USH2A mutation

B Dreyer et al. Am J Hum Genet. 2001 Jul.

Erratum in

Abstract

Usher syndrome type IIa is an autosomal recessive disorder characterized by mild-to-severe hearing loss and progressive visual loss due to retinitis pigmentosa. The mutation that most commonly causes Usher syndrome type IIa is a 1-bp deletion, described as "2299delG," in the USH2A gene. The mutation has been identified in several patients from northern and southern Europe and from North America, and it has been found in single patients from South America, South Africa, and China. Various studies have reported a range of frequencies (.16-.44) among patients with Usher syndrome, depending on the geographic origin of the patients. The 2299delG mutation may be the one that most frequently causes retinitis pigmentosa in humans. Given the high frequencies and the wide geographic distribution of the mutation, it was of interest to determine whether the mutation resulted from an ancestral mutational event or represented a mutational hotspot in the USH2A gene. Haplotype analysis was performed on DNA samples from 116 unrelated patients with Usher syndrome type IIa; the patients were from 14 countries and represented 148 2299delG alleles. On the basis of six single-nucleotide polymorphisms within the USH2A gene, 12 core haplotypes were observed in a panel of normal chromosomes. However, in our analysis, only one core haplotype was found to be associated with the 2299delG mutation. The data indicate that the widespread geographic distribution of the 2299delG mutation is the result of an ancestral mutation that has spread throughout Europe and into the New World as a result of migration.

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Figures

Figure 1

Figure 1

Relative locations of the SNPs and the 2299delG mutation within the USH2A gene and the three selected flanking markers. Exons 1–21 are depicted as boxes and are numbered intermittently, for the sake of legibility. We used distance estimates that were derived from Weston et al. (2000) and the Genome Database.

References

Electronic-Database Information

    1. Genome Database, http://www.gdb.org (for genotyping of markers)
    1. Hereditary Hearing Loss Home Page (G. Van Camp, R. J. H. Smith), http://www.uia.ac.be/dnalab/hhh/
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for Usher syndrome [MIM <276900>])

References

    1. Adato A, Weston MD, Berry A, Kimberling WJ, Bonne-Tamir A (2000) Three novel mutations and twelve polymorphisms identified in the USH2A gene in Israeli USH2 families. Hum Mutat 15:388 - PubMed
    1. Beneyto MM, Cuevas JM, Millan JM, Espinos C, Mateu E, Gonzalez-Cabo P, Baiget M, Domenech M, Bernal S, Ayuso C, Garcia-Sandoval B, Trujillo MJ, Borrego S, Antinolo G, Carballo M, Najera C (2000) Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II (USH2). Ophthalmic Genet 21:123–128 - PubMed
    1. Boughman JA, Vernon M, Shaver KA (1983) Usher syndrome: definition and estimate of prevalence from two high-risk populations. J Chronic Dis 36:595–603 - PubMed
    1. Dreyer B, Tranebjærg L, Rosenberg T, Weston MD, Kimberling WJ, Nilssen Ø (2000) Identification of novel USH2A mutations: implications for the structure of USH2A protein. Eur J Hum Genet 8:500–506 - PubMed
    1. Eudy JD, Weston MD, Yao S, Hoover DM, Rehm HL, Ma-Edmonds M, Yan D, Ahmad I, Cheng JJ, Ayuso C, Cremers C, Davenport S, Möller C, Talmadge CB, Beisel KW, Tamayo M, Morton CC, Swaroop A, Kimberling WJ, Sumegi J (1998) Mutation of a gene encoding a protein with extracellular matrix motifs in Usher syndrome type IIa. Science 280:1753–1757 - PubMed

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