Autosomal Recessive Hereditary Congenital Aplasia of the Vasa Deferentia in four Siblings

Schellen, Ton M.C.M.; Straaten, Antoine van

doi:10.1016/s0015-0282(16)45030-2

Cited by 31 publications

(10 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The majority of males with CF (>95%) suffer from this form of infertility, therefore it appears that the male reproductive tract is extremely sensitive to CFTR mutations. Indeed, the clinical spectrum affecting the male reproductive tract and associated with defects in the CFTR gene is extending beyond CF in the form of isolated congenital bilateral absence of vas deferens (CBAVD) [71]. The G-P studies for male infertility are discussed in the next section.…”

Section: How Do Cftr Mutations Contribute To Clinical Variation In Cf?mentioning

confidence: 99%

Genotype and Phenotype in Cystic Fibrosis

2000

View full text Add to dashboard Cite

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cAMP-induced chloride channel and appears capable of regulating other ion channels. Besides the most common mutation, ΔF508, accounting for about 70% of CF chromosomes worldwide, more than 850 mutant alleles have been reported to the CF Genetic Analysis Consortium. These mutations affect CFTR through a variety of molecular mechanisms which can produce little or no functional CFTR at the apical membrane. This genotypic variation provides a rationale for phenotypic effects of the specific mutations. The extent to which various CFTR alleles contribute to clinical variation in CF is evaluated by genotype-phenotype studies. These demonstrated that the degree of correlation between CFTR genotype and CF phenotype varies between its clinical components and is highest for the pancreatic status and lowest for pulmonary disease. The poor correlation between CFTR genotype and severity of lung disease strongly suggests an influence of environmental and secondary genetic factors (CF modifiers). Several candidate genes related to innate and adaptive immune response have been implicated as pulmonary CF modifiers. In addition, the presence of a genetic CF modifier for meconium ileus has been demonstrated on human chromosome 19q13.2. The phenotypic spectrum associated with mutations in the CFTR gene extends beyond the classically defined CF. Besides patients with atypical CF, there are large numbers of so-called monosymptomatic diseases such as various forms of obstructive azoospermia, idiopathic pancreatitis or disseminated bronchiectasis associated with CFTR mutations uncharacteristic for CF. The composition, frequency and type of CFTR mutations/variants parallel the spectrum of CFTR-associated phenotypes, from classic CF to mild monosymptomatic presentations. Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology.

show abstract

Section: How Do Cftr Mutations Contribute To Clinical Variation In Cf?mentioning

confidence: 99%

Genotype and Phenotype in Cystic Fibrosis

2000

View full text Add to dashboard Cite

show abstract

“…This situation of more than one brother being afflicted with CBAVD is probably not rare, as the frequency of this happening should approach 25070 if there is an identified index male sibling in the family. Sporadic reports have documented the existence of such brothers [28]. If a sister has inherited both mutations, she may not have any sign or symptom of CF, as the fallopian tubes (the counterpart of the internal male ductal system) are not anatomically affected in CF and fertility is not compromised.…”

Section: Genetic Implicationsmentioning

confidence: 99%

Congenital bilateral absence of the vas deferens and cystic fibrosis

Oates

Amos

1993

World J Urol

View full text Add to dashboard Cite

CF and CBAVD are really just ends of a clinical spectrum. The type and nature of the mutations in the CF gene probably determine the phenotypic expression of the patient. Perhaps all patients homozygous for delta F508, for example, will have severe pulmonary and pancreatic disease as well as absent vasa, whereas those with other combinations, such as delta F508/D1270N, will be unaffected in terms of pulmonary and pancreatic function but will have absent vasa. Besides contributing to a better understanding of the nature of CBAVD, this linkage of CF and CBAVD most importantly mandates genetic screening and counseling for appropriate family members and even the patient's spouse. In addition, a broader understanding of CF is now at hand, as this brings a whole new cohort of patients under the CF umbrella. Many of these will have at least one, if not two, rare or novel CF gene mutations. Once all of these mutations have been detected and defined, our knowledge of the CF gene, its mutations, and their implications will be dramatically expanded.

show abstract

“…CBAVD (McKusick 277180) has long been noted as a frequent cause of male infertility that is inherited in an autosomal recessive fashion (Nelson 1950;Schellen and van Stratten 1980); it occurs in 1%-2% of men presenting with infertility at urological departments and may have an incidence of up to 1:1000 in Caucasian males (Charny and Gillenwater 1965;Dubin and Amelar 1971;Holsclaw et al 1971;Jequier et al 1985;Oates and Amos 1994;Mak and Jarvi 1996). Although isolated CBAVD is considered a distinct clinical and genetic entity, it was suggested as long ago as 1971 that some males with CBAVD may have an unusually mild form of CF (Holsclaw et al 1971).…”

Section: Introductionmentioning

confidence: 99%

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens

et al. 1997

View full text Add to dashboard Cite

Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%-2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the "5T" allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none was compound heterozygous for delta F508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for delta F508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the "5T allele" was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.

show abstract

Autosomal Recessive Hereditary Congenital Aplasia of the Vasa Deferentia in four Siblings

Cited by 31 publications

References 4 publications

Genotype and Phenotype in Cystic Fibrosis

Genotype and Phenotype in Cystic Fibrosis

Congenital bilateral absence of the vas deferens and cystic fibrosis

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens

Contact Info

Product

Resources

About