ABCMdb

PMID: 8644747

Witt DR, Schaefer C, Hallam P, Wi S, Blumberg B, Fishbach A, Holtzman J, Kornfeld S, Lee R, Nemzer L, Palmer R
Cystic fibrosis heterozygote screening in 5,161 pregnant women.
Am J Hum Genet. 1996 Apr;58(4):823-35., [PubMed]

Sentences

No. Mutations Sentence Comment

11 ABCC7 p.Arg117His The incidence of R117H mutations was much higher than expected. Login to comment 69 ABCC7 p.Gly551Asp ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr Lab group A was screened for the 6 most common mutations (F508, G542X, G551D, R553X, W1282X, and N1303K); lab group B was screened for 12 mutations, including the 6 most common and an additional 6 less common alleles (R117H, 621+1, I507, 1717G-A, R560T, and S549N). Login to comment 142 ABCC7 p.Arg117His ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Ser549Asn ABCC7 p.Arg560Thr Table 7 CFTR Mutations in Screened Women NUMBER (%) wITH MUTATIONa GROUP ETHNiciTY F508 G542X GS5lD R553X W1282X N1303K R117H 621+1 1507 1717G-A R560T S549N TOTAL A Caucasian 26 (81) 5 (16) 1 (3) NA NA NA NA NA NA 32 Hispanic 2 (100) NA NA NA NA NA NA 2 B Caucasian 63b (65) 4 (4) 2 (3) 1 (1) 2 (2) 4 (4) 16b (16) 4 (4) 1 (1) 97b Hispanic 7 (88) 1 (12) 8 Caucasian/ Hispanic 2 (50) 1 (25) 1 (25) 4 'NA = not applicable. Login to comment 145 ABCC7 p.Arg117His Unexpectedly, R117H was present in very high frequency in Caucasians and accounts for 16% of all carriers in lab group B. Login to comment 150 ABCC7 p.Arg117His ABCC7 p.Arg560Thr Seven heterozygotes were identified: 4 F508s and 1 each of R117H, 1717G-A, and R560T. Login to comment 158 ABCC7 p.Arg117His The compound heterozygote identified through screening was a 36-year-old woman with the F508 and R117H mutations. Login to comment 165 ABCC7 p.Gly551Asp ABCC7 p.Arg117His Mutation analysis revealed both boys to be compound heterozygotes for G551D and R117H. Login to comment 172 ABCC7 p.Arg117His ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Factors that potentially contributed to the high rate of acceptance in this study included incorporation of pretest education into an ex- Table 8 Results of Prenatal Diagnosis in High-Risk Pregnancies CFTR MUTATIONSa COUPLE PRENATAL DIAGNOSIS Mother Father Fetus 1 No (miscarriage) GSS1D R117H N/GSS1D (abortus) 2 No (miscarriage) F508 1717G-A NA 3 No (miscarriage) F508 RS60T NA Yes (second pregnancy) N/N 4 Yes G542X F508 N/N S Yes F508 F508 N/F508 6 Yes (twins) F508 F508 F508/F508, F508/F508 7 Yes F508 F508 N/N 8b Yes F508 NA N/F508 9b Yes N1303K NA N/N1303K a NA = not available; and N = normal. Login to comment 207 ABCC7 p.Arg117His This rate is higher than anticipated, largely because of the unexpected high frequency of R117H in 16% of carriers, which represents a 16-fold increase over that seen in CF Consortium data (Tsui 1992). Login to comment 208 ABCC7 p.Arg117His ABCC7 p.Arg117His This rate is higher than anticipated, largely because of the unexpected high frequency of R117H in 16% of carriers, which represents a 16-fold increase over that seen in CF Consortium data (Tsui 1992). Login to comment 209 ABCC7 p.Arg117His ABCC7 p.Arg117His Because the R117H missense mutation is associated with a milder so-called pancreatic sufficient phenotype (Kristidis et al. 1992; Gervais et al. 1993), it is possible that this allele is underrepresented in the Consortium data, which is comprised of clinically diagnosed CF patients. An additional explanation is suggested by the identification ofa variable poly T region at the CFTR splice site at exon 9, which modifies the functional efficiency of the protein (Chu et al. 1993). Login to comment 210 ABCC7 p.Arg117His ABCC7 p.Arg117His ABCC7 p.Arg117His As has been reported elsewhere (Klesewetter et al. 1993), all of the R117H heterozygotes identified in our study have the more efficient 7T region, in contrast to a group of clinically diagnosed CF patients in which ST predominates. Login to comment 211 ABCC7 p.Arg117His ABCC7 p.Arg117His Thus, the lower frequency of R117H in the Consortium data may be a consequence of failure to ascertain most individuals with R117H and the more efficient splicing mechanism. Login to comment 212 ABCC7 p.Arg117His The presence of the R117H mutation in all three of these individuals is consistent with its mild diminution in CFTR protein expression and the potential ameliorating effect of the variable exon 9 splice site (Chu et al. 1993; Chillon et al. 1995). Login to comment 213 ABCC7 p.Arg117His The presence of the R117H mutation in all three of these individuals is consistent with its mild diminution in CFTR protein expression and the potential ameliorating effect of the variable exon 9 splice site (Chu et al. 1993; Chillon et al. 1995). Login to comment 270 ABCC7 p.Arg117His Med Care 29:473-489 Gervais R, Dumur V, Rigot J-M, Lafitte J-J, Roussel P (1993) High frequency of the R117H mutation in patients with congenital absence of the vas deferens. N Engl J Med 328:446-447 Gilbert F (1990) Is population screening for cystic fibrosis appropriate now? Login to comment 271 ABCC7 p.Arg117His Med Care 29:473-489 Gervais R, Dumur V, Rigot J-M, Lafitte J-J, Roussel P (1993) High frequency of the R117H mutation in patients with congenital absence of the vas deferens. N Engl J Med 328:446-447 Gilbert F (1990) Is population screening for cystic fibrosis appropriate now? Login to comment