ABCMdb

PMID: 10970190

Boyne J, Evans S, Pollitt RJ, Taylor CJ, Dalton A
Many deltaF508 heterozygote neonates with transient hypertrypsinaemia have a second, mild CFTR mutation.
J Med Genet. 2000 Jul;37(7):543-7., [PubMed]

Sentences

No. Mutations Sentence Comment

509 ABCC7 p.Arg117His In addition, three transiently hypertrypsinaemic babies who would otherwise have qualified for the cohort had already been identified as compound heterozygotes for F508/R117H CF mutations through extended mutation analysis of their parents. Login to comment 522 ABCC7 p.Arg117His R117H was the most common second mutation found, constituting 45% of the compound heterozygotes identified. Login to comment 526 ABCC7 p.Arg117His Recent work has suggested that "polyvariant mutant CFTR genes" may, when combined, result in less functional or pathologically insuYcient CFTR.21 In the light of this, we determined the incidence of the intronic poly-T tract, IVS8-nT, which interacts with the R117H mutation. Login to comment 532 ABCC7 p.Arg117His In general, the severity of lung disease is less predictable than the degree of pancreatic involvement.22 The R117H has been associated with a range of phenotypes and the intronic variant polyT tract (IVS8-nT) is known to aVect expression. Login to comment 533 ABCC7 p.Arg117His The IVS8-5T variant is an ineYcient splice acceptor site and with R117H, in trans with F508, results in a pancreatic suYcient phenotype. Login to comment 534 ABCC7 p.Arg117His The 7T variant and R117H combination in F508 heterozygotes is associated with congenital bilateral absence of the vas deferens and, in some cases, mild lung disease.19 23 Some females with this genotype are completely asymptomatic. Login to comment 538 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Pro67Leu ABCC7 p.Arg117Leu ABCC7 p.Phe1052Val ABCC7 p.Arg75* ABCC7 p.Arg75* ABCC7 p.Arg1066His ABCC7 p.Arg851* ABCC7 p.Leu967Ser ABCC7 p.Phe693Leu These have been reported in patients with presenting phenotypes ranging from "cystic fibrosis" to oligospermia, but there have been too few cases Table 2 Compound heterozygotes detected Domain and mutation type Genotype Exon 1st IRT 2nd IRT Transmembrane, missense F508/P67L 3 129 34* F508/R117H 4 110 21* F508/R117H 4 84 34 F508/R117H 4 95 39 F508/R117H 4 104 40 F508/R117H 4 146 41 F508/R117H 4 104 48* F508/R117H 4 120 53 F508/R117H 4 111 54 F508/R117H 4 175 72* F508/R117L 4 129 70 F508/L967S 15 122 15 F508/F1052V 17b 189 29 F508/R1066H 17b 94 18 Transmembrane, nonsense F508/R75X 3 86 26 F508/R75X 3 171 27 F508/R851X 14a 112 76 Regulatory, missense F508/F693L 13 109 29 Alternate splice site F508/3849+10KB C→T i19 99 26* F508/3849+10KB C→T i19 112 36* None of these samples had the IVS8-5T variant sequence. Login to comment 543 ABCC7 p.Phe693Leu The missense mutation F693L is located in the regulatory domain of CFTR and was first identified in a young girl with F508 on her other allele who was diagnosed with pancreatic insuYcient cystic fibrosis.26 Three subjects had nonsense mutations which are normally associated with severe disease as they introduce a stop codon, leading to truncated, usually inactive, CFTR protein being transcribed. Login to comment