CFTR Gene Variants and Genotypes in Russian Patients with CBAVD Syndrome

Russian Journal of Genetics - CBAVD syndrome is one of the common genetic causes of male infertility, associated with obstructive azoospermia, commonly resulting from pathogenic CFTR gene variants....     

Evaluation of clinical significance of с.2956G&gt;A (rs112287730) polymorphism in <Emphasis Type="Italic">FBN1</Emphasis> gene in Marfan syndrome

Marfan syndrome (MFS) is an autosomal dominant inherited systemic disorder of connective tissue with many clinical manifestations in the cardiovascular, skeletal, and ocular systems. MFS is caused by mutations in the fibrillin-1 (FBN1) gene. To date, about 2000 FBN1 pathogenic variants that cause MFS or related phenotypes have been described. The c.2956G>A, p.Ala986Thr substitution (exon 25) in the FBN1 gene is described in the SNP database as rs112287730 with allele frequency of 0.02%. Although numerous published data exist, the clinical significance of this variant is unknown. Some studies identify this substitution as probably a pathogenic mutation, and others, as a polymorphism. Among Russian Marfan patients, the heterozygous c.2956G>A substitution was identified in four probands; three of them had familial history. To determine the clinical significance of this substitution, a segregation analysis of DNA samples of affected and unaffected family members was conducted. In the first case, a segregation of the c.2956G>A substitution with the disease was observed in the family: this substitution was detected in the heterozygous state in the three affected members, but not in the one unaffected member. However, the opposite observation occurred in the second familial case: three affected members did not have the c.2956G>A substitution, whereas it was found in one unaffected member. In addition, the molecular-genetic analysis of 110 ethnically unrelated unexplored individuals was performed. The c.2956G>A substitution was identified in two of 220 examined chromosomes (allele frequency 0.9%). Thus, it was established that the c.2956G>A substitution appears to be a polymorphism (nonpathogenic variant) and cannot cause MFS.