ABCMdb

PMID: 16973827

Radpour R, Gourabi H, Gilani MA, Dizaj AV, Rezaee M, Mollamohamadi S
Two novel missense and one novel nonsense CFTR mutations in Iranian males with congenital bilateral absence of the vas deferens.
Mol Hum Reprod. 2006 Nov;12(11):717-21. Epub 2006 Sep 14., [PubMed]

Sentences

No. Mutations Sentence Comment

10 ABCC7 p.Thr338Ala ABCC7 p.Lys536* ABCC7 p.Tyr122His This approach allowed us to detect one novel nonsense mutation (K536X) in the nucleotide-binding domain 1 (NBD1) region and two novel missense mutations (Y122H and T338A) in the M2 and M6 regions of CFTR gene in our studied population, which were not reported previously. Login to comment 12 ABCC7 p.Lys536* K536X nonsense mutation (transversion) was found in the first NBD (NBF1), which plays an important regulatory role in CFTR function. Login to comment 14 ABCC7 p.Thr338Ala ABCC7 p.Tyr122His Because Y122H and T338A mutations were compound heterozygote with the IVS8-5T, it is difficult to judge the severity of these mutations and their role in the CBAVD phenotype. Login to comment 21 ABCC7 p.Arg117His The most common mutations found in isolated CBAVD phenotypes are F508del, R117H and the T5 allele (IVS8-T5) (Chillon et al., 1995; Jarvi et al., 1995). Login to comment 45 ABCC7 p.Thr338Ala ABCC7 p.Lys536* ABCC7 p.Tyr122His Mutation Location Mutation type Nucleotide alteration Allele frequency (%) K536X Exon 11 Nonsense 1738 A to T 1/224 (0.45) Y122H Exon 4 Missense 496 T to C 1/224 (0.45) T338A Exon 7 Missense 1144 A to G 1/224 (0.45) Figure 1. Login to comment 46 ABCC7 p.Lys536* (A) Trans-abdominal/rectal ultrasonography in Patient no. 103 with one K536X mutation showed absence of the vas deferens and seminal vesicles (white arrows) (left) with right kidney agenesis (right). Login to comment 47 ABCC7 p.Tyr122His (B) Trans-abdominal ultrasonography in Patient no. 100 with Y122H and IVS8-5T mutations. Login to comment 48 ABCC7 p.Thr338Ala (C) Transabdominal ultrasonography in Patient no. 49 with T338A and IVS8-5T mutations. Login to comment 68 ABCC7 p.Tyr122His The second mutation was a transition mutation of 496T→C in exon 4 (Figure 2) which causes amino acid change of tyrosine to histidine at position 122 of the CFTR polypeptide. Login to comment 73 ABCC7 p.Thr338Ala mutation of 1144A→G in exon 7 (Figure 2) which causes an amino acid change of threonine to alanine at position 338 of CFTR polypeptide. Login to comment 78 ABCC7 p.Thr338Ala ABCC7 p.Thr338Ala ABCC7 p.Lys536* ABCC7 p.Tyr122His ABCC7 p.Tyr122His The numbering of the reported mutations is as follows: c.1738A>T or p.Lys536Stop (K536X), c.496T>C or p.Tyr122His (Y122H) and c.1144A>G or p.Thr338Ala (T338A). Login to comment 79 ABCC7 p.Lys536* PTT analysis for nonsense mutation PTT analysis results confirmed that K536X is a nonsense mutation. Login to comment 89 ABCC7 p.Lys536* K536X An exon 11 nonsense mutation (transversion) was found in the NBF1 domain. Login to comment 95 ABCC7 p.Lys536* Therefore, the K536X considered as a severe allele responsible for obstructive azoospermia. Login to comment 96 ABCC7 p.Tyr122His Y122H A nucleotide substitution (transition) in exon 4 was compound heterozygote with IVS8-5T in a patient (Patient no. 100) who presented obstructive azoospermia with hypoplastic vas deferens diagnosed on clinical palpation. Login to comment 98 ABCC7 p.Tyr122His Y122H is located in TMD-M2. Login to comment 104 ABCC7 p.Thr338Ala T338A An exon 7 missense mutation in TMD-M6 was found with 1144A→G in a CBAVD phenotype (Patient no. 49). Login to comment 105 ABCC7 p.Thr338Ala T338A was Table II. Login to comment 110 ABCC7 p.Thr338Ala ABCC7 p.Lys536* ABCC7 p.Tyr122His Mutation type IVS8-(TG)mTn M470V n (%) K536X (TG)10 9T / (TG)10 9T M/V 1 (0.89) Y122H (TG)11 7T / (TG)13 5T V/V 1 (0.89) T338A (TG)11 7T / (TG)13 5T M/V 1 (0.89) Figure 3. Login to comment 121 ABCC7 p.Thr338Ala ABCC7 p.Tyr122His Because Y122H and T338A mutations were compound heterozygote with the IVS8-5T, it is difficult to judge the severity of these mutations and their role in the CBAVD phenotype. Login to comment