The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis

Genet Med. 2002 Sep-Oct;4(5):319-23. doi: 10.1097/00125817-200209000-00001.

Abstract

Purpose: To determine whether intragenic changes modulate the cystic fibrosis (CF) phenotype in individuals who are positive for the I148T allele.

Methods: The genes from individuals who carried at least one copy of the I148T allele were analyzed for additional changes that may be acting as genetic modifiers.

Results: Seven of eight individuals with a known or suspected diagnosis of CF who carried I148T in combination with a severe CF mutation also carried 3199del6. Eight apparently healthy adult individuals who were compound heterozygous for I148T and a severe CF mutation or homozygous for I148T did not carry the deletion ( = 0.0014). The I148T allele occurs on at least three haplotypes: an IVS-8 9T background, a 7T background, or a 9T + 3199del6 background. The 3199del6 allele was not identified in 386 non-CF chromosomes.

Conclusions: It is concluded that I148T occurs on at least three haplotypes and the complex allele I148T + 9T + 3199del6 is associated with a classic CF phenotype.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • DNA Mutational Analysis
  • Gene Deletion
  • Gene Expression
  • Haplotypes / genetics*
  • Humans
  • Incidence
  • Infant
  • Infant, Newborn
  • Middle Aged
  • Mutation / genetics*

Substances

  • CFTR protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator