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.
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.
Authors: Els Dequeker; Manfred Stuhrmann; Michael A Morris; Teresa Casals; Carlo Castellani; Mireille Claustres; Harry Cuppens; Marie des Georges; Claude Ferec; Milan Macek; Pier-Franco Pignatti; Hans Scheffer; Marianne Schwartz; Michal Witt; Martin Schwarz; Emmanuelle Girodon Journal: Eur J Hum Genet Date: 2008-08-06 Impact factor: 4.246
Authors: Charles M Strom; Richard Janeszco; Franklin Quan; Sheng-biao Wang; Arlene Buller; Matthew McGinniss; Weimin Sun Journal: J Mol Diagn Date: 2006-07 Impact factor: 5.568
Authors: C Castellani; H Cuppens; M Macek; J J Cassiman; E Kerem; P Durie; E Tullis; B M Assael; C Bombieri; A Brown; T Casals; M Claustres; G R Cutting; E Dequeker; J Dodge; I Doull; P Farrell; C Ferec; E Girodon; M Johannesson; B Kerem; M Knowles; A Munck; P F Pignatti; D Radojkovic; P Rizzotti; M Schwarz; M Stuhrmann; M Tzetis; J Zielenski; J S Elborn Journal: J Cyst Fibros Date: 2008-05 Impact factor: 5.482