• PMID: 31356021
• Gene Name: CFTR
• Condition: Male infertility
• Association: Associated
• Mutation: F508del, CFTRdel21kb, 1677delTA, 2143delT, W1282X and 5T
• Population size: 885
• Population details: 885 infertile men
• Sex: Male
• Infertility type: Male infertility
• Associated genes: Snapshot PCR

[The incidence of AZF deletions, CFTR mutations and long alleles of the ar CAG repeats during the primary laboratory diagnostics in a heterogeneous group of infertily men]

Mikhaylenko DS, Sobol IY, Safronova NY, Simonova OA, Efremov EA, Efremov GD, Alekseev BY, Kaprin AD, Nemtsova MV.

AIM: microdeletions in the AZF region of Y-chromosome, compound heterozygotes of severe and mild CFTR mutations, and long CAG-repeats in the androgen receptor gene (AR) as marker of predisposition are frequently studied as genetic causes of male infertility. A simultaneously testing of the panel including biochemical, immunological, cyto- and molecular genetic markers is often performed during the complex laboratory diagnostics in infertile men. The aim of our work was to identify molecular genetic alterations, which are advisable for simultaneously testing in a man with currently uncertain form of infertility, to increase the informativeness of laboratory diagnostics. MATERIALS AND METHODS: a retrospective study of 885 infertile men was conducted. AZF deletions were determined by multiplex PCR using 10 STS-markers (sY83, sY84, sY86, sY127, sY134, sY143, sY152, sY157, sY254, sY255) and two control loci SRY and AMEL with detection in polyacrylamide gel. Mutations in the CFTR gene (F508del, CFTRdel2.3(21kb), I507del, 1677delTA, 2143delT, 2184insA, 394delTT, W1282X, G542X, N1303K, R334W and 5T) were detected by PCR and SNaPshot. For determination of length of the AR CAG-repeat a fragment analysis of fluorescently labeled PCR products on the 3500xl capillary sequencer was performed. RESULTS: AZF deletions were detected in 8.2% of cases. The largest number of deletions was found in the AZFc subregion (58.9%), while a frequency of deletion in AZFa, AZFb or combined deletions of two and three subregions was 5.5%, 12.3% and 23.3%, respectively. Heterozygous carriage of severe CFTR mutations was detected in 4.7% patients. The most frequent mutation was F508del (83.3%), followed by CFTRdel21kb (7.1%) and W1282X (4.8%). The frequency of the mild splicing 5T mutation was 5.3%, and its incidence was significantly higher than in the previously published control group (p=0.002). AR genotyping revealed that the most prevailing allele was 21 (CAG) (21.5%). Long alleles with 27 or more CAG-trinucleotides were identified in 7.5% of the tested cases. In addition, 7 CAG heterozygotes with Kleinfelter syndrome were found. CONCLUSION: during primary complex laboratory diagnostics in a heterogeneous group of infertile men, it is advisable to detect AZF deletions and the most frequent CFTR mutations, including F508del, CFTRdel21kb, 1677delTA, 2143delT, W1282X and 5T. The more comprehensive analysis of CFTR mutations is justified only in patients with verified obstructive infertility. Sequencing of panels associated with infertility genes using NGS technology is promising. FAU - Mikhaylenko, D S AU - Mikhaylenko DS AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Sobol, I Y AU - Sobol IY AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Safronova, N Y AU - Safronova NY AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Simonova, O A AU - Simonova OA AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Efremov, E A AU - Efremov EA AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Efremov, G D AU - Efremov GD AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Alekseev, B Y AU - Alekseev BY AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia. FAU - Kaprin, A D AU - Kaprin AD AD - I.M. Sechenov First Moscow State Medical University (Sechenov University. AD - Moscow, Russia. AD - N.A. Lopatkin Research Institute of Urology and Interventional Radiology branch of the National Medical Research Radiologial Center. AD - Moscow, Russia. AD - Research Centre for Medical Genetics. AD - Moscow, Russia.