ABCMdb

PMID: 22842702

Ni WH, Jiang L, Fei QJ, Jin JY, Yang X, Huang XF
The CFTR polymorphisms poly-T, TG-repeats and M470V in Chinese males with congenital bilateral absence of the vas deferens.
Asian J Androl. 2012 Sep;14(5):687-90. doi: 10.1038/aja.2012.43. Epub 2012 Jul 30., [PubMed]

Sentences

No. Mutations Sentence Comment

8 ABCC7 p.Arg117His It is estimated that about one in 20-25 Caucasians carries a mutation of the CFTR gene.2 In contrast, CF is very rare in Asian populations including Chinese.3-5 However, congenital bilateral absence of the vas deferens (CBAVD) is not uncommon in Asian populations.6 CBAVD accounts for approximately 6% of cases of obstructive azoospermia7 and is responsible for 1%-2% of all infertility in males.6 It is well known that CBAVD is also present in nearly 95% of all CF males.6 To date, more than 1000 mutations have been identified in the CFTR gene in classic and atypical CF patients worldwide.8 Mutations of the CFTR gene have also been frequently reported in patients with CBAVD.6 In the majority of cases, CBAVD can be considered to be an atypical, genital phenotypic presentation of CF, presenting without other clinical manifestations of CF.9 The 5T allele, R117H and F508del, are the most common CFTR mutations in Caucasian CBAVD patients.2 The poly(T) sequence located in the splicing acceptor site of intron 8 (IVS8 poly(T)) has three variants, with five, seven or nine thymidines (the 5T, 7T and 9T alleles, respectively).10 The 7T or 9T allele generate a predominantly normal mRNA transcript, whereas the 5T variant affects splicing efficiency and results in reduced levels of normal mRNA due to deletion of exon 9.11 The protein product of the CFTR transcript lacking exon 9 is devoid of cyclic adenosine monophosphate-activated chloride conductance, and therefore, the 5T allele is now considered as a mild mutation with an incomplete penetrance.11,12 Prior studies have demonstrated that the disease penetrance of 5T depends on the copy number of its adjacent TG repeats.13,14 The number of TG repeats immediately adjacent to 5T is associated with a variable efficiency of exon 9 splicing.15,16 The different alleles at (TG)m(T)n polymorphic loci at the 39 end of human CFTR intron 8 determine the exon 9 splicing efficiency.17,18 In other respects, the M470V (1540A/G in exon 10) polymorphism is one of the most common polymorphisms in the CFTR gene.19 By in vitro studies, it was shown that the CFTR gene carrying the V allele yielded a lower functional CFTR protein rate than those carrying the M allele, independently of the intron 8 Tn genotype.15 de Meeus et al.19 reported that strong linkage disequilibrium was observed between the 5T allele and the V allele of the M470V polymorphism in the CBAVD population, but not in the normal population. Login to comment 50 ABCC7 p.Arg117His The frequency of IVS8-5T in our patients was higher than in Portuguese (27.4%),24 Iranian (25.94%),25 Chinese residents of Taiwan (29.2%)26 and Turkish patients (19.6%).27 The compound heterozygote with a major mutation of CFTR such as F508del or R117H, which causes the development of CBAVD in Caucasian populations, determined the pathogenic 5T allele.10 However, no major CFTR mutations, such as F508del, were found in Japanese and Chinese residents of Taiwan subjects with CBAVD.6 In our study, we also found no F508del mutation in Chinese population with CBAVD. Login to comment 103 ABCC7 p.Pro1290Ser N Engl J Med 1995; 332: 1475-80. 24 Grangeia A, Carvalho F, Fernandes S, Silva J, Sousa M et al. A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens. Login to comment 107 ABCC7 p.Pro1290Ser N Engl J Med 1995; 332: 1475-80. 24 Grangeia A, Carvalho F, Fernandes S, Silva J, Sousa M et al. A novel missense mutation P1290S at exon-20 of the CFTR gene in a Portuguese patient with congenital bilateral absence of the vas deferens. Login to comment