ABCMdb

PMID: 9917439

Wilschanski M, Rivlin J, Cohen S, Augarten A, Blau H, Aviram M, Bentur L, Springer C, Vila Y, Branski D, Kerem B, Kerem E
Clinical and genetic risk factors for cystic fibrosis-related liver disease.
Pediatrics. 1999 Jan;103(1):52-7., [PubMed]

Sentences

No. Mutations Sentence Comment

32 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* The correlation between liver disease and CF genotype was studied in seven mutations associated with the severe phenotype: ⌬F508, R553X, 1717-1G-ϾA, G542X, W1282X, N1303K, and G551D.2,14 No significant cor- From the *Department of Pediatrics, Cystic Fibrosis Center, Shaare Zedek Medical Center, Hebrew University, Jerusalem; ‡Cystic Fibrosis Center, Carmel Medical Center, Haifa; §Cystic Fibrosis Center, Sheba Medical Center, Tel Hashomer; ࿣Cystic Fibrosis Center, Schneider Children`s Medical Center, Petah Tikva; ¶Cystic Fibrosis Center, Soroka Medical Center, Ben Gurion University, Beer Sheba; #Cystic Fibrosis Center, Rambam Medical Center, Haifa; **Cystic Fibrosis Center, Hadassah University Hospital, Jerusalem; ‡‡Department of Medical Statistics, Ichilov Medical Center, Tel Aviv; and §§Department of Genetics, Life Sciences Institute, Hebrew University, Jerusalem, Israel. Login to comment 50 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* Forced expiratory volume in 1 second, and forced vital capacity, were measured and expressed as a percentage of predicted values for height and sex, using previously described standardized pulmonary equations.17 Current height and weight percentiles were computed using the tables of Tanner.18 Mutation Analysis All the patients were screened for all of the CFTR mutations previously identified in the Israeli CF population.15,16 Patients were classified according to severity of genotype: patients with severe genotype were homozygous or compound heterozygous to ⌬F508, W1282X, G542X, N1303K, 405ϩ1G3A, delTATT 4010, 1717-1G-ϾA. Login to comment 51 ABCC7 p.Gly85Glu These mutations were shown to be associated with PI, early age at diagnosis, higher sweat chloride level, and lower current age.3,4 Patients with the milder genotype carried the mutation 3849ϩ10kb C-ϾT, which was shown to be associated with increased incidence of PS, later age at diagnosis, higher current age, normal or intermediate range sweat chloride levels, and male fertility.19,20 Patients with a variable genotype were homozygous or compound heterozygous for the G85E mutation, or compound heterozygous for the 5T allele that may present with either severe or milder phenotype.6,7 Unclassified genotypes were mutations which, because of the small number of patients, have not been sufficiently characterized. Login to comment 114 ABCC7 p.Gly85Glu However, patients carrying the variable genotype (G85E or 5T,6,7 ), which is also associated with high rate of PS, had a Fig 1. Login to comment 117 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Ser549Arg ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Gly85Glu ABCC7 p.Tyr1092* ABCC7 p.Tyr1092* ABCC7 p.Trp1089* ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys Classification of Identified Genotype According to Severity of Disease Severe n Milder n Variable n Unclassified n ⌬F508/⌬F508 52 3849 ϩ 10kbC 3 T/⌬F508 7 ⌬F508/G85E 1 S549R/S549R 1 W1282X/W1282X 30 3849 ϩ 10kbC 3 T/405 ϩ 1G3A 3 G85E/G85E 5 S549R/G542X 2 ⌬F508/W1282X 39 3849 ϩ 10 kbC 3 T/W1282X 7 G85E/5T 1 S549R/W1282X 1 ⌬F508/G542X 10 3849 ϩ 10kbC 3 T/G85E 1 ⌬F508/5T 1 ⌬F508/W1089X 1 W1282X/G542X 12 W1282X/5T 2 Y1092X/Y1092X 1 W1282X/N1303K 7 W1282X/5T 1 Q359K-T360K/? Login to comment 118 ABCC7 p.Trp1282* ABCC7 p.Trp1089* 2 W1282X/405 ϩ 1G3A 1 5T/W1089X 2 ⌬F508/? Login to comment 120 ABCC7 p.Trp1282* 3 W1282X/? Login to comment 121 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* 12 N1303K/T4010 2 G542X/? Login to comment 122 ABCC7 p.Asn1303Lys ABCC7 p.Gly542* 3 N1303K/G542X 3 405 ϩ 1G3A/? Login to comment 123 ABCC7 p.Trp1282* ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Asn1303Lys ABCC7 p.Gly542* ABCC7 p.Gly542* ABCC7 p.Thr360Lys ABCC7 p.Thr360Lys ABCC7 p.Gln359Lys ABCC7 p.Gln359Lys 1 N1303K/N1303K 6 Q359K-T360K/ 4 Q359K-T360K ⌬F508/405 ϩ 1G3A 5 W1282X/1717-1G 3 A 1 G542X/G542X 1 N1303K/1717-1G 3 A 1 Total 173 18 16 36 ARTICLES high prevalence of liver disease. Login to comment 129 ABCC7 p.Arg117His The coexistence of two independent DNA alterations in the same CFTR allele might modulate the phenotype.30 Variations in intronic signals for splicing of CFTR transcripts, such as the 5T allele in intron 8 of the CFTR gene, were shown to affect the disease severity of patients carrying the R117H mutation.31 However, in our study no other CFTR mutation was found in the same CFTR alleles of the 3849ϩ10kb C-ϾT mutation that were in all the patients associated with the 7T variant. Login to comment 132 ABCC7 p.Arg117His Therefore, the extrapolation of our results onto other populations who have a higher incidence of other mild mutations such as R117H requires further studies. Login to comment