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Congenital Bilateral Absence (congenital + bilateral_absence)
Selected AbstractsA T3 allele in the CFTR gene exacerbates exon 9 skipping in vas deferens and epididymal cell lines and is associated with Congenital Bilateral Absence of Vas Deferens (CBAVD),HUMAN MUTATION, Issue 1 2005Antoine Disset Abstract The different alleles at the (TG)m(T)n polymorphic loci at the 3, end of the human CFTR intron 8 determine the efficiency by which exon 9 is spliced. We identified a novel TG12T3 allele in a congenital bilateral absence of vas deferens (CBAVD) patient who carries a [TG11T7; p.Phe508Cys; p.Met470Val] haplotype on the other chromosome. To better understand the complex regulation of exon 9 splicing, we analyzed the levels of correctly spliced CFTR transcripts in six CFTR-expressing epithelial cell lines derived from lung, colon, testis, vas deferens, and epididymis transiently transfected with four CFTR minigenes (pTG11T7, pTG12T7, pTG12T5, and pTG12T3). In this work, we show that a decrease in the Ts at the polymorphic locus in a TG12 background determines a cell-type dependent reduction in exon 9+ transcripts that is not related to the basal splicing efficiency in the cell line. These data emphasize the role of the T5 allele in CBAVD and identify the T3 allele as a severe cystic fibrosis (CF) disease-causing mutation. Finally, UV cross-linking experiments demonstrated that tissue-specific trans -acting splicing factors do not contribute to the different patterns of exon 9 splicing found between the cell lines. However, we observed that lower numbers of Ts can alter the binding of TDP-43 (TDP43 or TARDBP) to its specific target ug12 in a tissue-specific manner. Our results support the idea that the ratio of general splicing factors plays a role in the tissue variability of exon 9 alternative splicing. Hum Mutat 25:72,81, 2005. © 2004 Wiley-Liss, Inc. [source] Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation associated with a congenital bilateral absence of vas deferensINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2008Hideo Sakamoto Abstract: Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations associated with cystic fibrosis have been reported to be rare in Japanese patients with congenital bilateral absence of vas deferens (CBAVD). A 28-year-old Japanese male was referred for infertility. Vas deferens and epididymis were not palpable bilaterally. Semen analyses showed azoospermia with volumes below 2.0 ml. Serum follicle-stimulating hormone value was slightly elevated. Seminal fructose concentration was also very low. Scrotal ultrasonography showed absence of the bodies and tails of the right and left epididymides. Imaging studies showed cystic dysplasia of the right seminal vesicle and agenesis of the left seminal vesicle. A CFTR gene mutation of I556V was found. Recent studies show that prevalence of CFTR gene mutation in Japanese CBAVD patients may be approximately equal to that of the Caucasian population. Genetic counselling may be recommended for any couple attempting assisted reproduction technology when the man has CBAVD. [source] Clinical findings in congenital absence of the vasa deferentiaANDROLOGIA, Issue 1 2000Dr W.-H. Summary. In a clinical study, 105 patients with congenital bilateral absence of the vas deferens (CBAVD) and 18 with congenital unilateral absence of the vas deferens (CUAVD) were investigated. CUAVD was observed on the left side in 66%. Renal agenesis was more frequent in CUAVD (73.7%) than in CBAVD (11.8%). The leading signs of CBAVD are low pH level (average 6.5) and low volume of the ejaculate (average 0.95 ml). Testicular biopsies of 52 patients revealed normal spermatogenesis or hypospermatogenesis (33% in CBAVD; 45% in CUAVD). Genetic probing and counselling concerning cystic fibrosis are necessary if extracorporal microfertilization is considered. The absence of the vas deferens was often overlooked by the first investigator, the average time until correct diagnosis being 4.3 years. As artificial reproduction technology becomes more common, detection of vasal agenesis will certainly be made earlier and more frequently in the future. In order to assure compatibility of subsequent prospective studies about CBAVD and CUAVD, the following investigations are considered to be necessary: (i) semen analysis (pH, volume); (ii) renal ultrasonography or excretory urogram (screening for renal agenesis); (iii) genetic cystic fibrosis screening. [source] | ||||||||||