ABCMdb

ABCC7 p.Asn287Lys

ClinVar:	c.861C>G , p.Asn287Lys ? , not provided c.859A>T , p.Asn287Tyr ? , not provided
CF databases:	c.859A>T , p.Asn287Tyr (CFTR1) ? , This individual was a compound heterozygote for [delta]F508. He was diagnosed at 3 1/2 years of age when referred because of rectal prolapse; his sweat Cl was 75 and 81 mEq/L. He had been totally healthy since birth with normal growth and no significant gastrointestinal complaints. He had 4-5 upper respiratory infections per year. Formal pancreatic function testing was within normal limits. A vas deferens was identified on the side of the herniorraphy. He has grown along the fiftieth percentile for weight and the ninetieth for height without the use of pancreatic enzyme supplements. N287Y was originally identified by SSCA and HA and was subsequently detected by artificial Dra I site generating PCR amplification. c.861C>G , p.Asn287Lys (CFTR1) ? ,
Predicted by SNAP2:	A: D (63%), C: D (75%), D: D (66%), E: D (75%), F: D (80%), G: D (63%), H: D (71%), I: D (80%), K: N (57%), L: D (80%), M: D (85%), P: D (80%), Q: D (66%), R: D (80%), S: D (53%), T: D (53%), V: D (75%), W: D (91%), Y: N (53%),
Predicted by PROVEAN:	A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: D, K: N, L: D, M: N, P: D, Q: N, R: N, S: N, T: N, V: N, W: D, Y: N,

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[hide] Mutation spectrum of the CFTR gene in Taiwanese pa... Hum Reprod. 2005 Sep;20(9):2470-5. Epub 2005 May 19. Wu CC, Alper OM, Lu JF, Wang SP, Guo L, Chiang HS, Wong LJ
Mutation spectrum of the CFTR gene in Taiwanese patients with congenital bilateral absence of the vas deferens.
Hum Reprod. 2005 Sep;20(9):2470-5. Epub 2005 May 19., [PMID:15905293]

Abstract [show]
BACKGROUND: Clinically affected cystic fibrosis (CF) patients present a spectrum of genital phenotypes ranging from normal fertility to moderately impaired spermatogenesis and congenital bilateral absence of vas deferens (CBAVD). Little is known about the CF incidence in the Taiwanese population. It has been shown that the CBAVD in men without clinical evidence of CF is associated with a high incidence of mutated CFTR (cystic fibrosis transmembrane conductance regulator) alleles. In order to understand the involvement of the CFTR gene in the aetiology of Asian/Taiwanese male infertility, we screened the entirety of the CFTR gene in 36 infertile males with CBAVD. METHODS: Temporal temperature gradient gel electrophoresis (TTGE) followed by direct DNA sequencing was used. RESULTS: Five mutations, p.V201M, p.N287K, c.-8G > C (125G > C), p.M469I and p.S895N, were found in five of the patients. p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. In addition, seven homozygous and seven heterozygous 5T alleles in the intron 8 poly(T) tract were found. The overall frequency of CFTR mutant alleles in Taiwanese CBAVD males was 26 out of 72 = 36%. This finding was lower than the published frequency of CFTR mutations in other ethnic CBAVD patients (ranging from 50 to 74%). The frequency of p.M470V in Taiwanese CBAVD patients is not significantly different from that in the general population (P = 0.12). CONCLUSIONS: The results of this study add to the short list of Taiwanese/Asian CFTR mutations. Unlike Caucasian patients, the CFTR mutations cannot account for the majority of Taiwanese CBAVD. This is consistent with the low incidence of CF in the Asian/Taiwanese population. Furthermore, the mutation spectrum of CFTR in CBAVD patients does not overlap with the Caucasian CFTR mutation spectrum.

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No. Sentence Comment
39 However, no classic CF symptoms were identified in any of Table I. CFTR genotypes and clinical information in Taiwanese CBAVD patients PID Genotype IVS8 T n, (TG)n M470V Kidney Seminal vesicles Semen analyses pH Fructose Both alleles identified 1 10 IVS8-5T/IVS8-5T (TG)12 5T/(TG)12 5T V/V N BHy 2 34 IVS8-5T/IVS8-5T (TG)12 5T/(TG)13 5T M/V N BA 6.5 Neg 3 38 IVS8-5T/IVS8-5T (TG)12 5T/(TG)13 5T M/V N RA þ LHy 6 Neg 4 42 IVS8-5T/IVS8-5T (TG)13 5T/(TG)13 5T M/M 5 49 IVS8-5T/IVS8-5T (TG)12 5T/(TG)12 5T V/V 8 Pos 6 50 IVS8-5T/IVS8-5T (TG)12 5T/(TG)13 5T M/V 7 60 IVS8-5T/IVS8-5T (TG)12 5T/(TG)13 5T M/V One allele identified 8 18 N287K/? Login to comment
6 RESULTS: Five mutations, p.V201M, p.N287K, c.-8G > C (125G > C), p.M469I and p.S895N, were found in five of the patients. Login to comment
7 p.N287K occurred in the first transmembrane-spanning domain, p.M469I in the first ATP-binding domain and p.S895N in the second transmembrane-spanning domain, were novel. Login to comment
109 T) in the first ATP-binding fold, p.N287K (993C . Login to comment
114 The p.N287K mutation which changes a non-charged amino acid asparagine to a highly positively charged lysine in the hydrophobic transmembrane span is predicted to cause some structural/functional effect. Login to comment
158 G (p.N287K). Login to comment

[hide] Distribution of CFTR variations in an Indonesian e... Clin Infect Dis. 2010 May 1;50(9):1231-7. van de Vosse E, de Visser AW, Al-Attar S, Vossen R, Ali S, van Dissel JT
Distribution of CFTR variations in an Indonesian enteric fever cohort.
Clin Infect Dis. 2010 May 1;50(9):1231-7., 2010-05-01 [PMID:20233062]

Abstract [show]
BACKGROUND: Enteric fever is defined by circulating Salmonella serotype Typhi or Paratyphi in the blood. The first step in developing enteric fever is internalization of salmonellae in the gut epithelium. In in vitro experiments, attachment of S. Typhi to the cystic fibrosis transmembrane conductance regulator (CFTR) on the intestinal mucosa is crucial for bacterial uptake. We recently found a microsatellite polymorphism in the CFTR gene, IVS8CA, to be associated with susceptibility to enteric fever in a case-control study in Indonesia. METHODS: To determine which functional variation in CFTR is associated with susceptibility to enteric fever, we sequenced all 27 exons of the CFTR gene in 25 individuals from Indonesia. Polymorphisms that occurred more than once were genotyped in the full enteric fever cohort of 116 case patients and 322 control subjects. RESULTS: We identified 12 variants in, or adjacent to, the exons: 1 novel variant (L435V), 3 known mutations (N287K, I556V, Q1352H), and 8 known polymorphisms. Variations that occurred more than once were genotyped in the full cohort. The IVS8 TG(11)TG(12) genotype appears to provide some protection from acquiring enteric fever: having this protective genotype or a variation that is known to affect CFTR protein expression provides modest protection from enteric fever (odds ratio, 0.57; 95% confidence interval, 0.37-0.87; P<.01). CONCLUSIONS: The findings demonstrate that a correlation exists between variations in the CFTR gene and protection from enteric fever. The IVS8CA polymorphism that was identified previously may, however, be the principal functional variation causing the difference in susceptibility.

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No. Sentence Comment
8 We identified 12 variants in, or adjacent to, the exons: 1 novel variant (L435V), 3 known mutations (N287K, I556V, Q1352H), and 8 known polymorphisms. Login to comment
72 Variations Identified Once in 25 Sequenced Samples Variation SNP a Observed frequency Reported frequency of minor allele -8G1C in exon 1, 5`UTR rs1800501 1 in 50 (2%) 4.4% in Chinese, a 3.4% in Japanese, a 0%-4.5% in Europeans, a 0%-2.2% in Africans a 861C1G in exon 6b, leading to N287K NA 1 in 50 (2%) Found once in a Taiwanese CBAVD patient [12] 1303C1G in exon 9, leading to L435V NA 1 in 50 (2%) Novel variation, no data available 1666A1G in exon 11, leading to I556V NA 1 in 50 (2%) 2.6% in Koreans [11], 5.0% in Singapore Chinese [21] 3870A1G in exon 20, silent rs1800130 1 in 50 (2%) 0% in Chinese and in Japanese, a 0%-4.2% in Europeans, a 11.9%-21.2% in Africans a NOTE. CBAVD, congenital bilateral absence of the vas deferens; NA, not available; SNP, single-nucleotide polymorphism. Login to comment
134 Five of these were identified only once and were therefore not further analyzed in the full cohort, 2 of which, N287K and I556V, had been reported before as mutations and 1 of which, L435V, was identified for the first time. Login to comment
135 The mutation N287K has been reported once, in a patient with CBAVD from Taiwan [12]. Login to comment