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

Am J Hum Genet. 2001 Jul;69(1):228-34. doi: 10.1086/321269. Epub 2001 Jun 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Deafness / genetics*
  • Evolution, Molecular
  • Extracellular Matrix Proteins / genetics*
  • Founder Effect*
  • Gene Frequency / genetics*
  • Genetic Testing
  • Genotype
  • Geography
  • Haplotypes / genetics
  • Humans
  • Microsatellite Repeats / genetics
  • Mutagenesis / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Retinitis Pigmentosa / genetics*
  • Sequence Deletion / genetics*
  • Syndrome


  • Extracellular Matrix Proteins
  • USH2A protein, human