ABCMdb

PMID: 17394390

Lebo RV, Grody WW
Testing and reporting ACMG cystic fibrosis mutation panel results.
Genet Test. 2007 Spring;11(1):11-31., [PubMed]

Sentences

No. Mutations Sentence Comment

141 ABCC7 p.Gly542* Alternatively, when the genotype of a more closely related carrier has been reported, this information becomes the most informative (i.e., uncle is a ⌬F508 carrier rather than affected second cousin is a compound heterozygote for the ⌬F508 and the G542X mutations). Login to comment 154 ABCC7 p.Arg117His ABCC7 p.Arg117His Risks with R117H When the typically milder R117H mutation is found in the same allele as the 5T polythymidine tract upstream of the intron-8 splice site that reduces splicing efficiency, the two nucleotide modifications together usually result in a more severe CFTR allele. Login to comment 155 ABCC7 p.Arg117His Thus, the ACMG Cystic Fibrosis Committee recommended that all patients testing positive for the R117H mutation found in the 23-mutation panel have a reflex test for the 5T allele. Login to comment 157 ABCC7 p.Arg117His ABCC7 p.Arg117His However, a subsequent report found that even when R117H is found in trans (i.e., on a separate allele) from the 5T sequence, half of the compound heterozygotes with R117H mutations have elevated sweat tests and a proportion of these develop clinical disease (Massie et al. 2001). Login to comment 159 ABCC7 p.Arg117His ABCC7 p.Arg117His When the phase of the R117H and 5T sequences in one carrier parent is unknown and the other parent is unavailable for testing for CF carrier status, testing the fetus will not only reveal which CFTR allelic sequences the fetus carries but also determine the most likely phase of the R117H and 5T sequences in the known carrier parent. Login to comment 160 ABCC7 p.Arg117His Given both tests are accurate, when the fetus inherits the R117H allele without the 5T allele, the likelihood that these two alleles are not linked exceeds 99%. Login to comment 161 ABCC7 p.Arg117His ABCC7 p.Arg117His Alternatively, when the fetus inherits a 5T allele without the R117H allele, the likelihood the R117H and the 5T allele are not linked is 95% because the unavailable parent has a 10% likelihood of carrying a 5T allele, and there is a 50% likelihood of transmitting an existing allele to each offspring. Login to comment 162 ABCC7 p.Arg117His For the same reason, if the fetus inherits the R117H and 5T alleles, the likelihood that these were inherited on the same parental allele is 95%. Login to comment 178 ABCC7 p.Arg117His ABCC7 p.Arg117His If the untested U.S. Caucasian partner is negative for the 23-mutation test panel, the likelihood of having a fetus with CF is about 1 in 280, while the risk of having a child that is a carrier of a CF allele is equal to the reliability of the test for two CYSTIC FIBROSIS SCREENING 23 TABLE 5. AFTER-TEST RISKS: ASYMPTOMATIC WITH NEGATIVE FAMILY HISTORY AND PATIENT TESTING POSITIVE FOR BOTH THE R117H AND 5T SEQUENCES WHICH MAY BE ON ONE OR TWO CHROMOSOMES Carrier Carrier Fetal risk when the testing risk of untested partner shares positive with untested the same ethnicity Ethnic origin R117H and 5T partner as known carrier Northern 1/1 1/29 1/58 (1.7%) or European (100%) 3.4% 1/116 (0.9%) Caucasiana,b European 1/1 1/29 1/58 (1.7%) or Caucasian (100%) 3.4% 1/116 (0.9%) origin unspecified Ashkenazi 1/1 1/29 1/58 (1.7%) or Jewish (100%) 3.4% 1/116 (0.9%) Southern 1/1 1/29 1/58 (1.7%) or European (100%) 3.4% 1/116 (0.9%) Caucasiana Hispanic American 1/1 1/46 1/92 (1/1%) or (100%) 2.2% 1/184 (0.5%) African 1/1 1/65 1/130 (0.8%) or American (100%) 1.5% 1/260 (0.4%) Asian 1/1 1/90 1/180 (0.6%) or Americanc (100%) 1.1% 1/360 (0.3%) aNorthern Europe includes the Alps; southern Europe is south of the Alps. Login to comment 186 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His Genotypes R117H/R117H, 5T/5T, and R117H/⌬F508 have all been reported to result in CBAVD. Login to comment 187 ABCC7 p.Arg117His The R117H/⌬F508 genotype has also been found in CF patients with milder lung disease. Login to comment