Transmembrane Conductance Regulator Gene Mutations Research Articles

Cystic fibrosis transmembrane conductance regulator ( CFTR) gene mutations in Asians with chronic pulmonary disease: A pilot study

Background Little is known about the relationship between cystic fibrosis transmembrane conductance regulator ( CFTR) gene mutations in Asian patients and severe asthma or idiopathic bronchiectasis. We investigated this potential relationship in the Singaporean Chinese. Methods Twenty patients with chronic pulmonary disease, 14 with severe asthma and 6 with idiopathic bronchiectasis, were screened for CFTR mutations by direct gene sequencing. The frequencies of identified putative mutations were compared against 40 unaffected controls and 96 unselected population samples. Results Three missense mutations (I125T, I556V, and Q1352H) and 1 splice site variant (intron 8 12TG5T) were identified in a total of 10 patients, representing a combined mutant/variant allele frequency of 0.25. These alleles were also observed in the controls, but at a significantly lower allele frequency of 0.09 ( P < 0.01). Furthermore, the I125T mutation was significantly associated with the idiopathic bronchiectasis sub-group ( P < 0.05). Conclusions The significantly higher frequency of CFTR mutations among patients with chronic pulmonary disease compared with unaffected controls suggests that these mutations may increase risk for disease. The association of I125T with idiopathic bronchiectasis alone suggests that different mutations predispose to different disease.

Increased frequency of cystic fibrosis transmembrane conductance regulator gene mutations in infertile males

To investigate the frequency of mutations of the cystic fibrosis transmembrane regulator (CFTR) gene in males with reduced sperm quality before intracytoplasmic sperm injection (ICSI). The nine most frequent cystic-fibrosis-causing mutations in the German population and IVS8T alleles were analyzed. University-based centers for reproductive medicine and clinical genetics. An unselected group of 597 males with oligo-, astheno-, terato-, crypto-, oligoasthenoteratozoospermia, or azoospermia, which underwent pre-ICSI genetic counseling over a 5-year period. Blood samples were collected from the patients during genetic counseling. Frequency of mutations of CFTR gene in infertile males. A heterozygous CFTR mutation was observed in 34 of 597 patients (5.70%). None of the patients had two CFTR mutations. Given that our mutation panel recognizes about 82% of heterozygotes, it can be assumed that the frequency of CFTR heterozygotes in our cohort is about 6.94%. The frequency of CFTR mutations in our cohort did not correlate with a reduced sperm count. The frequency of cystic fibrosis in the German population is 1:3300. Thus, a CFTR heterozygosity of 3.42% can be estimated. This indicates that in our cohort of infertile males, the frequency of CFTR heterozygosity is twofold higher than in the general population (P<.0001).

Disruption of the SLC26A3-mediated anion transport is associated with male subfertility

Male subfertility in congenital chloride diarrhea (CLD) was possible after identification of expression of an epithelial Cl-/HCO3- exchanger SLC26A3 in the male reproductive tract and by the observation that adult men with CLD had very few children. A prospective clinical and laboratory study among eight adult Finnish men with CLD revealed constant oligoasthenoteratozoospermia but normal spermatogenesis, high chloride and low pH in seminal plasma, and three spermatoceles, suggesting that male subfertility is a clinical manifestation of CLD and could be caused by an analogous defect in the epithelial Cl-/HCO3- and water transport, as described for the CLD intestine.

The cystic fibrosis transmembrane conductance regulator gene and ion channel function in patients with idiopathic pancreatitis

Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations are associated with cystic fibrosis (CF)-related monosymptomatic conditions, including idiopathic pancreatitis. We evaluated prospectively enrolled patients who had idiopathic recurrent acute pancreatitis or idiopathic chronic pancreatitis, healthy controls, CF heterozygotes, and CF patients (pancreatic insufficient or sufficient) for evidence of CFTR gene mutations and abnormalities of ion transport by sweat chloride and nasal potential difference testing. DNA samples from anonymous blood donors were controls for genotyping. At least one CFTR mutation or variant was carried in 18 of 40 patients (45%) with idiopathic chronic pancreatitis and in 6 of 16 patients (38%) with idiopathic recurrent acute pancreatitis but in only 11 of the 50 controls (22%, P=0.005). Most identified mutations were rare and would not be identified in routine genetic screening. CFTR mutations were identified on both alleles in six patient (11%). Ion transport measurements in patients with pancreatitis showed a wide range of results, from the values in patients with classically diagnosed CF to those in the obligate heterozygotes and healthy controls. In general, ion channel measurements correlated with the number and severity of CFTR mutations. Twelve of 56 patients with pancreatitis (21%) fulfilled current clinical criteria for the diagnosis of CF, but CFTR genotyping alone confirmed the diagnosis in only two of these patients. We concluded that extensive genotyping and ion channel testing are useful to confirm or exclude the diagnosis of CF in the majority of patients with idiopathic pancreatitis.

CFTR Mutations

Acute pancreatitis (AP) is a rare association with Campylobacter jejuni (C. jejuni) enteritis. AP in association with another infectious illness like enteritis, may be related to an underlying genetic mutation. We report a patient with C. jejuni and AP, who was later found to have cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. A 15 yr old girl presented with abdominal pain and non bloody diarrhea for 8 days. She had a 5 lb weight loss, bilateral knee pain, 103.8°C fever and had used acetaminophen and ibuprofen. Past history was significant for poor growth, recurrent abdominal pain, and serum lipase elevated two fold normal on two occasions. Other tests in the past were a normal ultrasound and CT of abdomen, upper gastrointestinal and small bowel series, HIDA scan, celiac disease serology and duodenal biopsies. Sweat chloride test showed Na of 69 and Cl of 60 (N 0–40 mEq/L); pulmonary function tests, 72-h fecal fat, and fat soluble vitamin levels were normal. Family history revealed celiac disease in a cousin. She had unpasteurized milk 1 week prior to the acute illness. On admission her weight was <3% ile and exam revealed epigastric tenderness. Pertinent investigations were serum amylase of 103 (N < 90 IU/L) and lipase of 3,663 (N < 200 IU/L). Pain was managed with meperidine, feedings were held and intravenous fluids were started. Fasting lipid panel, repeat abdominal ultrasound and CT were normal. C. jejuni was detected on stool culture and she was treated with azithromycin for 7 days. She was pain free while she received nasojejunal nutrition with Ensure but notably serum amylase and lipase peaked to 554 & 21,047 respectively. Magnetic resonance cholangiopancreatography at this stage was normal. Furthermore, a buccal swab was performed for CF genetic mutation analysis; she was a compound heterozygote for R 117H, Δ F508 mutations. At 1 month follow-up, she remained asymptomatic on a regular diet and, serum amylase & lipase decreased to 308 & 650 respectively. CFTR mutations predispose to recurrent acute & chronic pancreatitis. In our patient with genetic predisposition to AP due to CFTR mutations, C. jejuni was thought to be an environmental modifier in initiating the acute episode.

Genotyping Microarray for the Detection of More Than 200 CFTR Mutations in Ethnically Diverse Populations

Cystic fibrosis (CF), which is due to mutations in the cystic fibrosis transmembrane conductance regulator gene, is a common life-shortening disease. Although CF occurs with the highest incidence in Caucasians, it also occurs in other ethnicities with variable frequency. Recent national guidelines suggest that all couples contemplating pregnancy should be informed of molecular screening for CF carrier status for purposes of genetic counseling. Commercially available CF carrier screening panels offer a limited panel of mutations, however, making them insufficiently sensitive for certain groups within an ethnically diverse population. This discrepancy is even more pronounced when such carrier screening panels are used for diagnostic purposes. By means of arrayed primer extension technology, we have designed a genotyping microarray with 204 probe sites for CF transmembrane conductance regulator gene mutation detection. The arrayed primer extension array, based on a platform technology for disease detection with multiple applications, is a robust, cost-effective, and easily modifiable assay suitable for CF carrier screening and disease detection.

Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosis

To determine which features of incomplete or "nonclassic" forms of cystic fibrosis (CF) are associated with deleterious CF transmembrane conductance regulator gene ( CFTR ) mutations, and to explore other etiologies for features not associated with deleterious CFTR mutations. Clinical features were compared between 57 patients with deleterious mutations in each CFTR and 63 with no deleterious mutations. The Shwachman Bodian Diamond syndrome gene ( SBDS ) was sequenced to search for mutations in patients with no deleterious CFTR mutations and steatorrhea to determine if any had unrecognized Shwachman-Diamond syndrome (SDS). The presence of a common CF-causing mutation, absence of the vas deferens, and Pseudomona aeruginosa in the sputum correlated with the presence of two deleterious CFTR mutations, whereas sweat chloride concentration, diagnostic criteria for CF, and steatorrhea did not. However, sweat chloride concentration correlated with CFTR mutation status in patients infected with P aeruginosa. One patient had disease-causing mutations in each SBDS . Presence of a common CF-causing mutation, absence of the vas deferens and/or P aeruginosa infection in a patient with features of nonclassic CF are predictive of deleterious mutations in each CFTR , whereas steatorrhea in the same context is likely to have etiologies other than CF transmembrane conductance regulator (CFTR) dysfunction.

Classic and nonclassic cystic fibrosis

Over the last few years, it has become apparent that the diagnosis of cystic fibrosis (CF) applies to an expanded phenotype. The term “nonclassic” CF has been introduced to describe a group of patients who do not have the full spectrum of abnormalities seen in “classic” CF. In this issue of The Journal, Groman and others report extensive phenotypic characterization and genetic analysis on 158 patients with nonclassic CF. Patients referred with one common CF mutation—absence of the vas deferens or P.aeruginosa in the sputum—were very likely to have a second CFTR mutation on detailed genetic analysis. By contrast, the concentration of chloride in sweat, the presence of clinical diagnostic criteria for CF, and the presence or absence of steatorrhea were not predictive for having two CF mutations. This study suggests that men who present with clinical features of nonclassic CF should be checked for absence of the vas deferens. Secondly, it indicates that patients with nonclassic CF and steatorrrhea should be studied for abnormalities in molecular mechanisms that do not affect CFTR. Over the last few years, it has become apparent that the diagnosis of cystic fibrosis (CF) applies to an expanded phenotype. The term “nonclassic” CF has been introduced to describe a group of patients who do not have the full spectrum of abnormalities seen in “classic” CF. In this issue of The Journal, Groman and others report extensive phenotypic characterization and genetic analysis on 158 patients with nonclassic CF. Patients referred with one common CF mutation—absence of the vas deferens or P.aeruginosa in the sputum—were very likely to have a second CFTR mutation on detailed genetic analysis. By contrast, the concentration of chloride in sweat, the presence of clinical diagnostic criteria for CF, and the presence or absence of steatorrhea were not predictive for having two CF mutations. This study suggests that men who present with clinical features of nonclassic CF should be checked for absence of the vas deferens. Secondly, it indicates that patients with nonclassic CF and steatorrrhea should be studied for abnormalities in molecular mechanisms that do not affect CFTR. Phenotypic and genetic characterization of patients with features of “nonclassic” forms of cystic fibrosisThe Journal of PediatricsVol. 146Issue 5PreviewTo determine which features of incomplete or “nonclassic” forms of cystic fibrosis (CF) are associated with deleterious CF transmembrane conductance regulator gene (CFTR) mutations, and to explore other etiologies for features not associated with deleterious CFTR mutations. Full-Text PDF

Lack of Association of Common Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations with Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic liver disease of uncertain etiology. However, the histologic features of PSC liver disease can resemble those in cystic fibrosis (CF), an inherited disorder caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We sought to determine if PSC patients have a higher frequency of common CF alleles than disease controls. DNA was extracted from peripheral lymphocytes of patients with end-stage liver disease. Samples were obtained before liver transplantation from 59 PSC patients and from three groups of control patients (20 each with primary biliary cirrhosis, autoimmune hepatitis, or hepatitis C). DNA samples were genotyped for 32 common CF mutations, the intron 8 T tract variants, and the M470V variant. One of 59 PSC patients (1.7%) had the common CF mutation (DeltaF508) in one CFTR gene. Two controls (3.3%) carried a single CF mutation (DeltaF508 in one primary biliary cirrhosis patient; W1282X in one hepatitis C patient). These rates do not differ from expected in the general population. The frequency of CFTR variants (5T and M470V) was also similar between PSC patients and controls. Despite anatomical similarities between CF liver disease and PSC, we could not confirm that PSC patients carried common CF mutations or common CFTR variants in higher than expected frequencies. These data suggest that CFTR dysfunction does not influence the pathogenesis of PSC.

Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Infertile Males with Congenital Bilateral Absence of the Vas Deferens

Congenital bilateral absence of the vas deferens (CBAVD) is characterized by azoospermia and male infertility. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with cystic fibrosis (CF), the most common autosomal recessive disorder in Caucasians. Recent publications on CBAVD raised the question whether CFTR gene mutations are responsible for CBAVD occurrence or not. This study was conducted to explore the role of CFTR gene mutations in the occurrence of CBAVD-dependent male infertility. Forty-four chromosomes of 22 CBAVD patients from Austrian ancestry were studied. For detection of the most common mutation DeltaF508, a deletion of phenylalanine at the 508th position of mature CFTR chloride channel protein, the 10th exon of the gene was screened by heteroduplex analysis. In order to identify non-DeltaF508 mutations, we also analyzed the entire coding regions, exon/intron boundaries of 27 exons and the 5'- and 3'-untranslated regions of the gene by denaturing gradient gel electrophoresis (DGGE) after polymerase chain reaction. All exons showing different banding patterns on the DGGE gels were sequenced to define existing DNA sequence variations. Among the analyzed 44 chromosomes of 22 patients, disease producing mutations were found in 31.8% (14/44). The most common mutation was DeltaF508 with a frequency of 43% (6/14), followed by R117H with 29% (4/14). Our results indicate that CFTR gene mutations are common but not the only reason for the occurrence of CBAVD-dependent male infertility. We recommend screening of the CFTR gene in these patients.

Molecular pathology of the CFTR locus in male infertility

Congenital bilateral absence of the vas deferens (CBAVD) is a form of infertility with an autosomal recessive genetic background in otherwise healthy males. CBAVD is caused by cystic fibrosis transmembrane conductance regulator ( CFTR) gene mutations on both alleles in approximately 80% of cases. Striking CFTR genotypic differences are observed in cystic fibrosis (CF) and in CBAVD. The 5T allele is a CBAVD mutation with incomplete penetrance. Recent evidence confirmed that a second polymorphic locus exists and is a major CFTR modifier. The development of minigene models have led to results suggesting that CFTR exon 9 is skipped in humans because of unusual suboptimal 5′ splice sites. An extremely rare T3 allele has been reported and it has recently been confirmed that the T3 allele dramatically increases exon 9 skipping and should be considered as a ‘CF’ mutation. Routine testing for the most prevalent mutations in the CF Caucasian population will miss most CFTR gene alterations, which can be detected only through exhaustive scanning of CFTR sequences. Finally, a higher than expected frequency of CFTR mutations and/or polymorphisms is now found in a growing number of monosymptomatic disorders, which creates a dilemma for setting nosologic boundaries between CF and diseases related to CFTR.

Etiology of azoospermia in 100 consecutive nonvasectomized men

History was taken systematically for 100 azoospermic, nonvasectomized men referred consecutively to a Danish fertility clinic. The men were examined by ultrasound, and their blood samples were analyzed for karyotype, Y microdeletions, and cystic fibrosis transmembrane conductance regulator gene mutations. In 29% of patients, the condition could be explained by genetic abnormalities; in 22%, by diseases or external influence; and in 27%, by former cryptorchidism. The azoospermic condition remained unexplained in only 22%.

High frequency of (TG) mT n variant tracts in the cystic fibrosis transmembrane conductance regulator gene in men with high semen viscosity

To evaluate a possible correlation between abnormal semen consistency and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and variant tracts. Study of CFTR mutations and variant tracts in men with high semen viscosity as compared with normospermic men. University-based centers for andrology, clinical biochemistry, and cystic fibrosis. Forty-six male partners from infertile couples with sine causa high semen viscosity compared with 72 normospermic men. Semen sample collection. We obtained the (TG)mTn polymorphic tracts and a panel of 31 mutations of CFTR, semen viscosity, and semen variables. The frequencies of the (TG)12 and T5 variant alleles were statistically significantly higher in men with high semen viscosity (17.4% and 7.6%, respectively) than in the normospermic control group (6.9% and 1.4%, respectively). The frequency of the genotypes carrying (TG)12 or T5 was statistically significantly higher in men with high semen viscosity (39.1%) than in the normospermic control group (16.7%). Four men with high semen viscosity showed the variant (TG)12T5 haplotype; one of these men presented variant tracts on both alleles. None of the normospermic controls showed a (TG)12T5 haplotype. Semen hyperviscosity could be considered a "minimal clinical expression" of cystic fibrosis; CFTR gene sequence variations may constitute the genetic basis for this disease.

Interleukin 8 secretion from monocytes of subjects heterozygous for the deltaF508 cystic fibrosis transmembrane conductance regulator gene mutation is altered.

Patients with cystic fibrosis (CF) exhibit an excessive host inflammatory response. The aim of this study was to determine (i) whether interleukin 8 (IL-8) secretion is increased from monocytes from subjects heterozygous as well as homozygous for cystic fibrosis transmembrane conductance regulator (CFTR) mutations and (ii) whether this is due to increased cell surface lipopolysaccharide (LPS) receptors or, alternatively, increased activation of mitogen-activated protein kinases (MAPK). The basal level of IL-8 secretion was higher from monocytes from CF patients than from monocytes from healthy controls (P = 0.02) and obligate heterozygotes (parents of the CF patients). The 50% effective concentrations for LPS-induced IL-8 production for monocytes from both CF patients and obligate heterozygotes were 100-fold lower than those for monocytes from healthy controls (P < 0.05). No differences in the levels of IL-1beta production were seen between these groups. Expression of the LPS surface receptors CD14 and Toll-like receptor 4 were not different between CF patients and healthy controls. In contrast, phosphorylation of the MAPKs p38 and ERK occurred at lower doses of LPS in monocytes from patients heterozygous and homozygous for CFTR mutations. These results indicate that a single allelic CFTR mutation is sufficient to augment IL-8 secretion in response to LPS. This is not a result of increased LPS receptor expression but, rather, is associated with alterations in MAPK signaling.

Atypical sinusitis in adults must lead to looking for cystic fibrosis and primary ciliary dyskinesia.

HYPOTHESES/OBJECTIVES:: In adults, purulent pansinusitis or nasal polyposis starting early in life or that is permanently infected or associated either with chronic bronchial infection, infertility, or situs inversus are uncommon. In these atypical cases of chronic sinusitis (ACS), a primary dysfunction of the mucociliary clearance can be suspected. Adult patients with ACS were therefore investigated to detect primary ciliary dyskinesia (PCD) or cystic fibrosis (CF). Open, prospective study. Forty-two patients with ACS were investigated with ciliary beat frequency and ultrastructure analysis in nasal cells and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis in blood leukocytes. The diagnosis of PCD was confirmed in seven (17%) patients. At least one CFTR gene mutation was detected in 16 (38%) patients. The diagnosis of CF was suggested in three (7%) compound heterozygous patients. Another 13 (31%) patients were heterozygous for a CFTR gene mutation or a complex allele. Comparison of clinical features of ACS showed that only a family history of chronic sinusitis (P <.01) or chronic bronchitis (P <.02) and the presence of diffuse bronchiectasis (P <.0001) or serous otitis media (P <.0001) were significantly more frequent in PCD patients than in patients carrying CFTR gene mutations or those without PCD or CFTR gene mutations. ACS should be considered a remarkable entity in which congenital abnormalities of epithelial cells are frequently detected (55% of patients). The higher frequency of mutations in ACS patients compared with the general population suggests that heterozygoty for CFTR gene mutation could be a sinusitis-causing status.

Multicenter characterization and validation of the intron-8 poly(T) tract (IVS8-T) status in 25 Coriell cell repository cystic fibrosis reference cell lines for cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation assays.

Cystic fibrosis (CF) is the most common life-limiting recessive genetic disorder in Caucasians, with a carrier frequency of ∼1 in 25 and incidence of ∼1 in 2500–3300 live births (1). CF is caused by mutations affecting the transmembrane conductance regulator (CFTR) gene localized on the long arm of chromosome 7 (7q31.2). CFTR contains 27 exons and encodes a protein of 1480 amino acids that functions as a cAMP-regulated chloride channel in the apical membrane of epithelial cells (2)(3). Mutations in the CFTR gene lead to dysfunction of the lungs, sweat glands, testes, ovaries, intestines, and pancreas. More than 1000 mutations in this gene have been identified to date (4). The clinical manifestations of the disease are variable, ranging from severe pulmonary disease with pancreatic insufficiency to mild pulmonary disease and pancreatic sufficiency (1). Moreover, mutations in the CFTR gene have also been found in patients who have normal lung function but show other clinical signs, such as congenital bilateral absence of the vas deferens (CBAVD), nasal polyposis, bronchiectasis, and bronchopulmonary allergic aspergillosis (5)(6). Some of the variability in the CF phenotype has been attributed to the influence of the 5T allele at a polymorphic poly(T) tract in intron 8 (IVS8-T) of the CFTR gene. Genotype–phenotype correlations have shown that there is a strong association of the 5T allele with male infertility caused by congenital CBAVD and with other monosymptomatic forms of CF, such as bronchiectasis and chronic idiopathic pancreatitis (5)(6 …

Current challenges in cystic fibrosis screening.

This article gives an overview of the symptoms and mutations associated with classic and atypical cystic fibrosis (CF). Current testing methods for mutation detection in CF are discussed. Review testing for CF, including American College of Medical Genetics and American College of Obstetrics and Gynecology guidelines and recommendations regarding population screening for CF. Describe symptomatic and mutational differences between patients with classic CF and atypical CF, including monosymptomatic conditions such as congenital bilateral absence of the vas deferens, idiopathic pancreatitis, and chronic sinusitis. Explain the concern about predicting the phenotypic expression of the condition from the genotype. Discuss the challenges of CF testing, including the preanalytic, analytic, and postanalytic phases. List the current methods for detecting CF transmembrane conductance regulator gene mutations, specifying the advantages and disadvantages of each. Describe the basic patient information necessary for laboratories to provide accurate risk assessments, such as ethnicity and family history, and reasons for the test being conducted (carrier or affected status). The technical challenges of detecting the 25 recommended mutations are being met by commercially available reagents. Challenges remain for the preanalytic and postanalytic phases. Only with accurate patient information can laboratories provide specific risk reductions on the basis of a negative genetic test result. As health care providers become better informed about the recommendations for CF testing and laboratories continue to increase the sensitivities of their assays, patients will benefit from increased screening efficiency and accuracy. This will allow affected individuals to receive prompt and effective treatment and carriers to enjoy an expanded number of reproductive options.

Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina.

The relationship between cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was examined. CFTR mutations have previously been associated with congenital bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in the vas deferens, a Wolffian duct derivative. Because the embryologic development of the Müllerian ducts directly depends on the prior normal development of the Wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. This study evaluated the role of CFTR mutations in the development of CAUV. DNA samples from 25 patients with CAUV were tested for the presence of 33 of the most common CFTR mutations. Protein-coding DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain reaction (PCR) and analyzed for mutations using allele-specific oligonucleotide (ASO) probes. Two patients were heterozygous for CFTR mutations. One was heterozygous for the W1282X mutation and the other was heterozygous for the DeltaF508 mutation. The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests that it is unlikely for CFTR mutations to cause CAUV in females as they cause CBAVD in some males. Furthermore, the data suggest that CAUV in females may be the same disorder as CBAVD in males who do not have CFTR mutations.

Association of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and primary sclerosing cholangitis (PSC)

Association of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and primary sclerosing cholangitis (PSC)

Clinical and genetic features of patients with congenital unilateral absence of the vas deferens

Objectives To review the clinical and genetic findings in men with congenital unilateral absence of the vas deferens (CUAVD). CUAVD is important because of its association with renal anomalies and cystic fibrosis transmembrane conductance regulator gene mutations. Methods A retrospective review of two urologic practices, both with subspecialty interest in male infertility, was performed. Renal imaging and cystic fibrosis (CF) testing were recommended to all men found to have CUAVD. Results Fifteen men with CUAVD were identified. Only the 12 men with sufficient clinical data were selected for this study. Three patients had CF mutations, and all had obstruction of the contralateral vas deferens in either the pelvis or retroperitoneum. One patient had obstruction of the contralateral pelvic vas deferens and was negative for all CF mutations tested. Four patients (33%) had renal agenesis. Three patients had ipsilateral renal agenesis, and one had contralateral renal agenesis. No patient with CF mutations had renal agenesis. One had polycystic kidney disease, which was considered an incidental finding. Conclusions Patients with CUAVD may have CF mutations and renal agenesis. Renal ultrasonography and CF testing are therefore recommended for these patients. Patients of reproductive age found to have CUAVD should be counseled about the potential risk of transmission of renal anomalies and CF mutations.