ABCMdb

PMID: 17823699

Pieri Pde C, Missaglia MT, Roque Jde A, Moreira-Filho CA, Hallak J
Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues.
Clinics (Sao Paulo). 2007 Aug;62(4):385-90., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCC7 p.Ser753Arg ABCC7 p.Gly149Trp RESULTS: Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis. Login to comment 34 ABCC7 p.Ser753Arg ABCC7 p.Ser753Arg The new mutation found in the patient is an AGC to AGG change in DNA leading to a serine-to-arginine substitution at position 753 (S753R) in the CFTR protein; S753 is a consensus phosphorylation site in the regulatory domain of CFTR protein.6 No other classical CFTR mutation was found, but a 5T allele was identified in intron 8 (IVS8-5T) together with an IVS8-9T in the other allele. Login to comment 41 ABCC7 p.Gly149Trp A glycine-to-tryptophan substitution at protein position 149 (G149W) was detected in both brothers. Login to comment 46 ABCC7 p.Ser753Arg ABCC7 p.Gly149Trp ABCC7 p.Gly149Trp Case 1 2a 2b Age 30y 32y 27y mutation S753R G149W G149W IVS8-Tn 5T/9T 5T/7T 5T/7T IVS8-TGm 10TG/12TG 10TG/11TG 10TG/11TG polymorphisms M470V M470V M470V 2694T>G 2694T>G Sweat chloride* 26nmol/L 24nmol/L 45nmol/L Seminal Vesicles right hypoplastic normal normal left hypoplastic agenesis agenesis *ref: normal<30nmol/L; borderline 30-60nmol/L; high >60nmol/L DISCUSSION Infertility is an important health problem, affecting 10% of all men in reproductive age around the world. Login to comment 54 ABCC7 p.Ser753Arg ABCC7 p.Gly149Trp In our study, we performed a screening of all the exons and splicing of sites of interest of the CFTR gene in eighteen CBAVD patients and two novel mutations were detected: a serine-to-arginine at an alternative phosphorylation site in the regulatory domain (S753R), and a glycine- to-tryptophan substitution at position 149 (G149W) in the second intracellular domain of the CFTR protein. Login to comment 56 ABCC7 p.Ser753Arg Considering the clinical presentation of the patient, S753R might not be a polymorphism once CBAVD was present together with a clear pulmonary phenotype, although not together with sweat-chloride elevation. Login to comment 57 ABCC7 p.Gly149Trp Besides, S753 is one of the ten serine residues submitted to phosphorylation (one in the NBD1 S-422 and nine in the R domain S-660, -670, -700, -712, -737, -753, -768, -795, -813) to exert the primary control of activation of Cl-conductance.27 The second novel mutation found was a G149W. Login to comment 58 ABCC7 p.Gly149Arg ABCC7 p.Gly149Arg A different mutation (G149R) at the same position was previously reported in a CBAVD patient11 but was not found in normal individuals nor in CF patients tested, placing the G149R in the category of Class V mutation usually associated to the CBAVD phenotype.11 The G to W substitution described here is probably even milder than G to R, once glycine and tryptophan are both not polar amino acids. Login to comment 59 ABCC7 p.Gly149Trp The presence of the same mutation in both brothers and the borderline sweat-chloride level found in one of them, favor G149W as a novel CBAVD Class V CFTR mutation. Login to comment 81 ABCC7 p.Ser753Arg ABCC7 p.Gly149Trp RESULTADOS: Foram identificadas duas muta&#e7;&#f5;es novas com altera&#e7;&#e3;o de amino&#e1;cidos (S753R and G149W) em 3 pacientes (dois irm&#e3;os) juntamente com o alelo IVS8-5T em heterozigose. Login to comment