ABCMdb

PMID: 11746017

White SM, Lucassen A, Norbury G
Cystic fibrosis: a further case of an asymptomatic compound heterozygote.
Am J Med Genet. 2001 Nov 1;103(4):342-3., 2001-11-01 [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Arg117His The R117H CFTR mutation, when found together with another CF mutation, has been associated with a variable phenotype ranging from classical CF to congenital bilateral absence of the vas deferens (CBAVD) [Gervais et al., 1993]. Login to comment 2 ABCC7 p.Arg117His We report on a healthy 29-year-old woman who was found to be a R117H/deltaF508 compound heterozygote of the CF gene but who was completely asymptomatic. Login to comment 9 ABCC7 p.Arg117His CF mutation analysis was undertaken as part of an evaluation for an egg donation program, and she was found to be a R117H/deltaF508 compound heterozygote of the CFTR gene. Login to comment 10 ABCC7 p.Arg117His This is the second reported case of an asymptomatic person with the genotype R117H/deltaF508 [Lee et al., 1992; Chmiel et al., 1999]. Login to comment 11 ABCC7 p.Arg117His Previous studies have shown that the length of the polythymidine tract in intron 8 of the CFTR gene is polymorphic and that particular lengths modulate the clinical effect of the R117H phenotype [Kiesewetter et al., 1993]. Login to comment 15 ABCC7 p.Arg117His The R117H mutation is a missense mutation in exon 4, which is at the external end of the second transmembrane domain of the CFTR protein and affects a basic amino acid that appears to reduce the conduction properties of the CFTR Cl-channel. Login to comment 16 ABCC7 p.Arg117His Since mRNAs lacking exon 9 generate CFTR proteins without chloride channel activity, it appears there may be a compounding effect between the shorter 5T tract and the R117H mutation. Login to comment 18 ABCC7 p.Arg117His In addition to the in¯uence of partially penetrant mutations, modi®ers and variable ef®ciency of splicing in different tissues also play some role in predicting the deltaF508/R117H phenotype. Login to comment 20 ABCC7 p.Arg117His The R117H mutation is found in the general population in cis with either a 5T, 7T, or, rarely, a 9T background. Login to comment 21 ABCC7 p.Arg117His ABCC7 p.Arg117His Kiesewetter et al. [1993] studied the polyT status of 38 pancreatic-suf®cient CF patients with the genotype R117H/deltaF508 and found 31 patients carried the 5T background with R117H and seven carried the 7T background. Login to comment 22 ABCC7 p.Arg117His ABCC7 p.Arg117His In eight patients with congenital bilateral absence of the vas deferens only, and in the single asymptomatic woman with R117H/ deltaF508, the 7T background was found with R117H in all cases. Login to comment 23 ABCC7 p.Arg117His Chmiel et al. [1999] reported a case of a female infant with the R117H/deltaF508 genotype ascertained through screening of parents during pregnancy. Login to comment 24 ABCC7 p.Arg117His The infant's genotype showed the 7T background was associated with the R117H mutation; no lung disease was present, the result of the sweat test was normal, and the child was thriving. Login to comment 26 ABCC7 p.Arg117His The woman, an R117H/deltaF508 compound heterozygote, showed no pulmonary or pancreatic disease and had normal sweat electrolytes. Login to comment 27 ABCC7 p.Arg117His In a further paper by the same group, Witt et al. [1996] reported the R117H mutation in this patient to be associated with the 7T background. Login to comment 28 ABCC7 p.Arg117His Thus, the polyT tract length and sex are important factors in¯uencing the pathogenic effect of the R117H mutation. Login to comment 29 ABCC7 p.Arg117His Rosenbluth and Goldenberger [1997] reported on a 70-year-old woman who was diagnosed with CF with a genotype R117H/deltaF508 and phenotype of chronic *Correspondence to: Dr. Login to comment 35 ABCC7 p.Arg117His The incidence of the R117H mutation in population screening studies has been found to be higher than that predicted by studies based on patients clinically diagnosed with CF [Tsui, 1992]. Login to comment 36 ABCC7 p.Arg117His In their study of over 5,000 pregnant women screened for CF mutations, Witt et al. [1996] found 16% carried the R117H mutation. Login to comment 37 ABCC7 p.Arg117His This is consistent with R117H in cis with 7T not being a fully penetrant mutation. Login to comment 38 ABCC7 p.Arg117His Analysis of the polythymidine tracts in our patient and in her parents showed that the R117H mutation was in cis with a 7T tract and the deltaF508 mutation in cis with a 9T tract. Login to comment 43 ABCC7 p.Arg117His This case report demonstrates the need for poly-T studies in any patient found to have the R117H mutation, and caution in the genetic counseling of such families. Login to comment