ABCMdb

PMID: 17489851

Tzetis M, Kaliakatsos M, Fotoulaki M, Papatheodorou A, Doudounakis S, Tsezou A, Makrythanasis P, Kanavakis E, Nousia-Arvanitakis S
Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cationic trypsinogen gene (PRSS1) to the etiology of recurrent pancreatitis.
Clin Genet. 2007 May;71(5):451-7., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Phe1052Val Two carried SPINK1 gene mutation p.N34S, one being transheterozygote with CFTR mutation p.F1052V. Login to comment 62 ABCC7 p.Arg1070Gln ABCC7 p.Phe1052Val ABCC7 p.Gly576Ala Molecular findings for the CFTR gene Eight patients were carriers (16%): three with p.R1070Q and five with p.F508del, p.G576A, p.F1052V, CFTRdel2,3 (21 kb), and c.2752215G/C, each, representing a heterozygote frequency 2.1-fold higher than that found in the 211 general population controls (7.6%, p , 0.0001). Login to comment 63 ABCC7 p.Arg334Trp ABCC7 p.Arg334Trp ABCC7 p.Arg347His ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg75Gln ABCC7 p.Glu822* ABCC7 p.Glu822* Nine patients (36%) were compound heterozygotes for two CFTR mutations, both mild (class IV or V): p.I148T/p.R75Q, c.278915G.A/p.R75Q or mild and severe: three with p.F508del/p.R334W and four withc.444delA/p.R334W,p.E822X/c.278915G.A, p.E822X/p.R347H and p.F508del/c.3272226A.G, each. Login to comment 72 ABCC7 p.Phe1052Val One patient was additionally transheterozygote for CFTR mutation p.F1052V. Login to comment 83 ABCC7 p.Arg334Trp ABCC7 p.Arg347His ABCC7 p.Arg75Gln ABCC7 p.Arg1070Gln This could especially apply for p.R334W, p.R347H, p.R1070Q, p.R75Q and c.278915G.A, for which the difference in mutation frequency between patients and classic CF cohort, reached statistical significance (Table 2). Login to comment 84 ABCC7 p.Ile148Thr It is especially of note that p.I148T in our patient cohort was not found linked to c.3199del6, which has been considered the classic CF causing allele (27). Login to comment 85 ABCC7 p.Arg117His Mutation CFTRdel2,3 (21 kb) considered a severe mutation and found once in our patient cohort, has been previously reported in an otherwise healthy 43-year-old woman, who presented with mild relapsing pancreatitis and had R117H in trans (28). Login to comment 87 ABCC7 p.Gly576Ala Mutation p.G576A, found in transheterozygote state with SPINK1 2253T/C promoter variant in our patient, has previously been reported in a CP patient, although the previous study did not screen the SPINK1 gene as well (16). Login to comment 88 ABCC7 p.Arg1070Gln The function modulating CFTR haplotypes (V470-TG11-T5 and V470-TG12-T7) were found either alone (patient 1650) or more commonly either in compound heterozygosity with p.R1070Q (patient 1523) or in trans-heterozygous state in two cases with c.272C/T SPINK1 variant (Table 1). Login to comment 90 ABCC7 p.Arg334Trp ABCC7 p.Arg347His ABCC7 p.Ile148Thr ABCC7 p.Arg75Gln ABCC7 p.Arg1070Gln ABCC7 p.Phe1052Val ABCC7 p.Gly576Ala Mutations and variants in the CFTR gene CFTR mutation/variant Patients with pancreatitis, n ¼ 25 (%) Controlsa , n ¼ 211 (%) Classic patients with CF, n ¼ 426 (%) p vs controls p vs patients with CF p.F508del 5 (10) 2 (0.47) 465 (54.6) ,0.0001 ,0.0001 p.R334W 4 (8) - 7 (8.2) 0.00011 0.0019 c.444delA 1 (2) - 1 (0.1) c.278915G.A 2 (4) - 11 (1.3) 0.011 CFTRdel2,3 (21 kb) 1 (2) - 2 (0.2) c.E822X 2 (4) - 12 (1.5) 0.011 p.R347H 1 (2) - - 0.055 p.R1070Q 3 (6) 1 (0.24) 7 (0.8) 0.004 0.013 p.G576A 1 (2) - 1 (0.1) p.F1052V 1 (2) 4 (0.95) 1 (0.1) p.I148T 1 (2) - 1 (0.1) c.3272226A.G 1 (2) - 7 (0.82) p.R75Q 2 (4) 4 (0.95) 1 (0.1) 0.0086 c.2752215G/C 1 (2) 4 (1) 5 (0.6) TG11T7 26 (52) 286 (67.7) ND TG11T5 2 (4) 5 (1.18) ND TG10T7 8 (16) 79 (18.7) ND TG10T9 8 (16) 14 (3.3) ND 0.0005 TG12T7 2 (4) 8 (1.9) ND M470 6 (12) 48 (11.4) ND V470 8 (16) 166 (39.3) ND 0.008 CF, cystic fibrosis; ND, not determined. Login to comment 93 ABCC7 p.Ala120Thr ABCC7 p.Arg297Gln ABCC7 p.Leu997Phe ABCC7 p.Arg1162Leu ABCC7 p.Glu826Lys ABCC7 p.Asp565Gly ABCC7 p.Ile807Met ABCC7 p.Cys491Ser ABCC7 p.Ser495Tyr a Additional mutations found in the controls: p.R1162L (1.66%), p.D565G (0.47%), p.A120T (0.47%) and 0.24% each for p.R297Q, p.L997F, p.E826K, p.I807M, p.S495Y and p.C491S. Login to comment 97 ABCC7 p.Phe1052Val We detected two heterozygotes (4%) for p.N34S mutation, cosegregating with IVS1237T.C one was additionally transheterozygote with CFTR mutation p.F1052V. Login to comment 99 ABCC7 p.Arg1070Gln ABCC7 p.Gly576Ala Promoter variant 2253T/C was detected in three patients all trans-heterozygotes with CFTR: two with p.R1070Q, and one with p.G576A. Login to comment 100 ABCC7 p.Arg334Trp The homozygous 2253C/C minor allele genotype was observed in one patient already CFTR compound heterozygous (p.F508del/p.R334W) (Table 1). Login to comment