ABCC7 p.Ile1366Phe
| CF databases: |
c.4097T>A
,
p.Ile1366Asn
(CFTR1)
?
,
c.4097T>C , p.Ile1366Thr (CFTR1) ? , Asymptomatic subject |
| Predicted by SNAP2: | A: D (75%), C: D (63%), D: D (91%), E: D (91%), F: D (71%), G: D (91%), H: D (85%), K: D (91%), L: D (59%), M: D (66%), N: D (85%), P: D (91%), Q: D (85%), R: D (91%), S: D (80%), T: D (71%), V: N (82%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Increased prevalence of CFTR mutations and variant... Hum Genet. 2003 Aug;113(3):286-92. Epub 2003 Jun 3. Sheth S, Shea JC, Bishop MD, Chopra S, Regan MM, Malmberg E, Walker C, Ricci R, Tsui LC, Durie PR, Zielenski J, Freedman SD
Increased prevalence of CFTR mutations and variants and decreased chloride secretion in primary sclerosing cholangitis.
Hum Genet. 2003 Aug;113(3):286-92. Epub 2003 Jun 3., [PMID:12783301]
Abstract [show]
Primary sclerosing cholangitis (PSC) and cystic fibrosis (CF) are both slowly progressive cholestatic liver diseases characterized by fibro-obliterative inflammation of the biliary tract. We hypothesized that dysfunction of the CF gene product, cystic fibrosis transmembrane conductance regulator (CFTR), may explain why a subset of patients with inflammatory bowel disease develop PSC. We prospectively evaluated CFTR genotype and phenotype in patients with PSC ( n=19) compared with patients with inflammatory bowel disease and no liver disease ( n=18), primary biliary cirrhosis ( n=17), CF ( n=81), and healthy controls ( n=51). Genetic analysis of the CFTR gene in PSC patients compared with disease controls (primary biliary cirrhosis and inflammatory bowel disease) demonstrated a significantly increased number of mutations/variants in the PSC group (37% vs 8.6% of disease controls, P=0.02). None of the PSC patients carried two mutations/variants. Of PSC patients, 89% carried the 1540G-variant-containing genotypes (resulting in decreased functional CFTR) compared with 57% of disease controls ( P=0.03). Only one of 19 PSC patients had neither a CFTR mutation nor the 1540G variant. CFTR chloride channel function assessed by nasal potential difference testing demonstrated a reduced median isoproterenol response of 14 mV in PSC patients compared with 19 mV in disease controls ( P=0.04) and 21 mV in healthy controls ( P=0.003). These data indicate that there is an increased prevalence of CFTR abnormalities in PSC as demonstrated by molecular and functional analyses and that these abnormalities may contribute to the development of PSC in a subset of patients with inflammatory bowel disease.
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No. Sentence Comment
83 S686Y and I1366F are novel potentially disease-causing variants that have not been reported from screening thousands of CF and healthy patients (http://www.genet.sickkids.on.ca/cftr/).
X
ABCC7 p.Ile1366Phe 12783301:83:10
status: NEW109 The remaining three PSC patients had potentially disease-causing mutations (S686Y, I1366F, R75Q), which may contribute to CF-like phenotypes.
X
ABCC7 p.Ile1366Phe 12783301:109:83
status: NEW[hide] Lack of association of common cystic fibrosis tran... Am J Gastroenterol. 2005 Apr;100(4):874-8. Gallegos-Orozco JF, E Yurk C, Wang N, Rakela J, Charlton MR, Cutting GR, Balan V
Lack of association of common cystic fibrosis transmembrane conductance regulator gene mutations with primary sclerosing cholangitis.
Am J Gastroenterol. 2005 Apr;100(4):874-8., [PMID:15784035]
Abstract [show]
BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease of uncertain etiology. However, the histologic features of PSC liver disease can resemble those in cystic fibrosis (CF), an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to determine if PSC patients have a higher frequency of common CF alleles than disease controls. METHODS: DNA was extracted from peripheral lymphocytes of patients with end-stage liver disease. Samples were obtained before liver transplantation from 59 PSC patients and from three groups of control patients (20 each with primary biliary cirrhosis, autoimmune hepatitis, or hepatitis C). DNA samples were genotyped for 32 common CF mutations, the intron 8 T tract variants, and the M470V variant. RESULTS: One of 59 PSC patients (1.7%) had the common CF mutation (DeltaF508) in one CFTR gene. Two controls (3.3%) carried a single CF mutation (DeltaF508 in one primary biliary cirrhosis patient; W1282X in one hepatitis C patient). These rates do not differ from expected in the general population. The frequency of CFTR variants (5T and M470V) was also similar between PSC patients and controls. CONCLUSIONS: Despite anatomical similarities between CF liver disease and PSC, we could not confirm that PSC patients carried common CF mutations or common CFTR variants in higher than expected frequencies. These data suggest that CFTR dysfunction does not influence the pathogenesis of PSC.
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No. Sentence Comment
104 The remaining four mutations included two novel variants S686Y and I1366F of unknown functional and phenotypic effect, a Table 4.
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ABCC7 p.Ile1366Phe 15784035:104:67
status: NEW106 of Classic CF Nonclassic CFTR Mutations Reference PSC Patients Mutations CF Mutations IVS8-5T of Unknown Effect McGill (1996) (21) 19 1 (G551D) 1 (R117H) NA NA Girodon (2002)(19) 29 0 3 (L997F, S1235R, D1270N) 2 1 (N782K) Sheth (2003)* (18) 19 0 3 (2752-26A→G, 3849 + 10kbC→T, I1139V) 1 3 (S686Y, I1366F, R75Q) Gallegos-Orozco (2004) 59 1 ( F508) 0 2 NA Total, no.
X
ABCC7 p.Ile1366Phe 15784035:106:311
status: NEW