ABCMdb

ABCC7 p.Lys1351Arg

ClinVar:	c.4051A>G , p.Lys1351Glu ? , not provided
CF databases:	c.4051A>G , p.Lys1351Glu (CFTR1) D , Missense mutation K1351E was identified in a German CBAVD patient who is heterozygous for this mutation and for [delta]F508.
Predicted by SNAP2:	A: D (85%), C: D (63%), D: D (95%), E: D (91%), F: D (91%), G: D (91%), H: D (85%), I: D (85%), L: D (85%), M: D (80%), N: D (91%), P: D (95%), Q: D (80%), R: N (82%), S: D (85%), T: D (85%), V: D (85%), W: D (91%), Y: D (91%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: N, F: D, G: D, H: D, I: D, L: D, M: D, N: D, P: D, Q: N, R: N, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Increased frequency of CFTR gene mutations identif... Gene. 2014 Sep 10;548(1):43-7. doi: 10.1016/j.gene.2014.07.005. Epub 2014 Jul 7. Sharma H, Mavuduru RS, Singh SK, Prasad R
Increased frequency of CFTR gene mutations identified in Indian infertile men with non-CBAVD obstructive azoospermia and spermatogenic failure.
Gene. 2014 Sep 10;548(1):43-7. doi: 10.1016/j.gene.2014.07.005. Epub 2014 Jul 7., [PMID:25010724]

Abstract [show]
High incidence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene is associated with congenital bilateral absence of the vas deferens (CBAVD) and is considered as the genital form of cystic fibrosis (CF). The CFTR gene may also be involved in the etiology of male infertility in cases other than CBAVD. The present study was conducted to identify the spectrum and frequency of CFTR gene mutations in infertile Indian males with non-CBAVD obstructive azoospermia (n=60) and spermatogenic failure (n=150). Conspicuously higher frequency of heterozygote F508del mutation was detected in infertile males with non-CBAVD obstructive azoospermia (11.6%) and spermatogenic failure (7.3%). Homozygous IVS(8)-5T allele frequency was also significantly higher in both groups in comparison to those in normal healthy individuals. Two mutations in exon 25 viz., R1358I and K1351R were identified as novel mutations in patients with non-CBAVD obstructive azoospermia. Mutation R1358I was predicted as probably damaging CFTR mutation. This is the first report from the Indian population, emphasizing increased frequency of CFTR gene mutations in male infertility other than CBAVD. Thus, it is suggested that screening of CFTR gene mutations may be required in infertile Indian males with other forms of infertility apart from CBAVD and willing for assisted reproduction technology.

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Sentences [show]
No. Sentence Comment
5 Two mutations in exon 25 viz., R1358I and K1351R were identified as novel mutations in patients with non-CBAVD obstructive azoospermia. Login to comment
87 SSCP analysis and subsequent DNA sequencing revealed two novel mutations viz., R1358I and K1351R (Table 2). Login to comment
88 Notably K1351R mutation was found in association with IVS8-5T allele in one patient. Login to comment
108 of alleles Non-CBAVD obstructive azoospermia (n = 60) T5 Reduction of oligo T tract to 5T at 1342-6 Aberrant splicing Intron 8 19 F508del Deletion of 3 bp (CTTor TTT) between 1652 and 1655 Deletion of phenylalanine at 508 Exon 11 7 R1358Ia G to A at 4073 Arginine to isoleucine at 1358 Exon 25 1 K1351Ra A to G at 4052 Lysine to arginine at 1351 Exon 25 1 Oligospermia/non-obstructive azoospermia (n = 150) T5 Reduction of oligo T tract to 5T at 1342-6 Aberrant splicing Intron 8 27 F508del Deletion of 3 bp (CTTor TTT) between 1652 and 1655 Deletion of phenylalanine at 508 Exon 10 11 a Indicates novel substitution mutations. Login to comment
137 Mutation Non-CBAVD obstructive azoospermia (OA) (n = 60) Spermatogenic failure (SF) (n = 150) Healthy control (ctrl) (n = 100) Chi square-test P valueÌe; OA vs ctrl SF vs ctrl OA vs SF 1 F508del 7 (11.6%) 11 (7.3%) 0 0.0008 0.008 NS 2 IVS(8)-5T homozygous 4 (6.6%) 7 (4.6%) 0 0.01 0.04 NS 3 IVS(8)-5T heterozygous 11 (18.3%) 13 (8.6%) 7 (7%) 0.00 NS 0.0001 4 R1358I 1 (1.6%) 0 0 NS - NS 5 K1351R 1 (1.6%) 0 0 NS - NS Ìe; P b 0.05 is considered as significant. Table 4 Pathological and stability prediction of novel substitution mutations identified in Indian non-CBAVD obstructive azoospermia patients. Login to comment
138 Pathological/structural prediction Novel mutants identified R1358I K1351R Polyphen score 1.00 0.03 Pathological prediction Probable damaging Benign iStable score 0.716 0.551 Stability prediction Decrease Unaffected Polyphen-2 (http://genetics.bwh.harvard.edu/pph2/) was used to generate the output score of novel sequence variants (threshold for pathological mutation was 0.05). Login to comment