12 research outputs found
Complex cytogenetic and molecular-genetic analysis of males with spermatogenesis failure
The chromosomal anomalies, microdeletions of AZF region of Y-chromosome and CFTR gene mutations have been studied among 80 infertile men with idiopathic spermatogenetic failure: 36 (45 %) patients with aspermia, 19 (24 %) patients with azoospermia and 25 (31 %) patients with severe oligoasthenoteratozoospermia. In total 30 % males with spermatogenetic failure genetic factor of infertility was observed. Karyotype anomalies were observed in 17.5 % of infertile men, within 16.2 % numerical and structural gonosomal anomalies and in 1.3 % β Robertsonian translocation were revealed. In 11 % males with spermatogenetic failure, Y-chromosome AZF region microdeletions were detected. The frequency of CFTR major mutation F508del among infertile men was 6.25 %. 5T allele of polymorphic locus IVS8polyT was detected in 7.5 % of examined men. The results obtained indicate the high complexity of cytogenetic and moleculargenetic studies of male infertility.ΠΠ·ΡΡΠ°Π»ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ, ΠΌΠΈΠΊΡΠΎΠ΄Π΅Π»Π΅ΡΠΈΠΈ AZF ΡΠ΅Π³ΠΈΠΎΠ½Π° Y-Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ ΠΈ ΠΌΡΡΠ°ΡΠΈΠΈ Π³Π΅Π½Π° Π’Π ΠΠ Ρ 80 ΠΌΡΠΆΡΠΈΠ½ Ρ ΠΈΠ΄ΠΈΠΎΠΏΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π°, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: Ρ 36 (45 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π°ΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ, 19 (24 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π°Π·ΠΎΠΎΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ ΠΈ 25 (31 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΎΠ»ΠΈΠ³ΠΎΠ°ΡΡΠ΅Π½ΠΎΡΠ΅ΡΠ°ΡΠΎΠ·ΠΎΠΎΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ IV ΡΡΠ΅ΠΏΠ΅Π½ΠΈ. Π ΠΎΠ±ΡΠ΅ΠΌ Ρ 30 % ΠΌΡΠΆΡΠΈΠ½ Ρ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π° ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ°ΠΊΡΠΎΡΡ Π±Π΅ΡΠΏΠ»ΠΎΠ΄ΠΈΡ. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ ΠΊΠ°ΡΠΈΠΎΡΠΈΠΏΠ° Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈ Ρ 17.5 % Π±Π΅ΡΠΏΠ»ΠΎΠ΄Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½, ΡΡΠ΅Π΄ΠΈ Π½ΠΈΡ
Ρ 16.2 % β ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΡΠ΅ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ ΠΈ Ρ 1.3 % β ΡΠΎΠ±Π΅ΡΡΡΠΎΠ½ΠΎΠ²ΡΠΊΡΡ ΡΡΠ°Π½ΡΠ»ΠΎΠΊΠ°ΡΠΈΡ. Π£ 11 % ΠΌΡΠΆΡΠΈΠ½ Ρ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π° Π²ΡΡΠ²ΠΈΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΠ΄Π΅Π»Π΅ΡΠΈΠΈ AZF ΡΠ΅Π³ΠΈΠΎΠ½Π° Y Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ. Π§Π°ΡΡΠΎΡΠ° ΠΌΠ°ΠΆΠΎΡΠ½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ F508del Π³Π΅Π½Π° Π’Π ΠΠ ΡΡΠ΅Π΄ΠΈ Π±Π΅ΡΠΏΠ»ΠΎΠ΄Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 6.25 %. 5T Π°Π»Π»Π΅Π»Ρ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΠ³ΠΎ Π»ΠΎΠΊΡΡΠ° IVS8polyT Π²ΡΡΠ²ΠΈΠ»ΠΈ Ρ 7.5 % ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ Π²ΡΡΠΎΠΊΠΎΠΉ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠ³ΠΎ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ ΠΌΡΠΆΡΠΊΠΎΠΌ Π±Π΅ΡΠΏΠ»ΠΎΠ΄ΠΈΠΈ
Cytogenetic and molecular analyses of de novo translocation dic(9;13)(p11.2;p12) in an infertile male
BACKGROUND: Whole arm t(9;13)(p11;p12) translocations are rare and have been described only a few times; all of the previously reported cases were familial. RESULTS: We present here an infertile male carrier with a whole-arm reciprocal translocation dic(9;13)(p11.2;p12) revealed by GTG-, C-, and NOR-banding karyotypes with no mature sperm cells in his ejaculate. FISH and genome-wide 400Β K CGH microarray (Agilent) analyses demonstrated a balanced chromosome complement and further characterised the abnormality as a dicentric chromosome (9;13): dic(9;13)(pterβp11.2::p12βqter),neo(9)(pterβp12βneoβp11.2). An analysis of the patientβs ejaculated cells identified immature germ cells at different phases of spermatogenesis but no mature spermatozoa. Most (82.5%) of the germ cells were recognised as spermatocytes at stage I, and the cell nuclei were most frequently found in pachytene I (41.8%). We have also undertaken FISH analysis and documented an increased rate of aneuploidy of chromosomes 15, 18, X and Y in the peripheral blood leukocytes of our patient. To study the aneuploidy risk in leukocytes, we have additionally included 9 patients with non-obstructive azoospermia with normal karyotypes. CONCLUSIONS: We propose that the azoospermia observed in the patient with the dic(9;13)(p11.2;p12) translocation was most likely a consequence of a very high proportion (90%) of association between XY bivalents and quadrivalent formations in prophase I
Contribution of chromosomal abnormalities and genes of the major histocompatibility complex to early pregnancy losses
Aim. The determination of chromosomal abnormalities in samples from early pregnancy losses and allelic polymorphism of HLAβDRB1 and DQA1 genes in couples with recurrent miscarriage. Methods. Banding cytogenetic and interphase mFISH analysis, DNA extraction by salting method, PCR, agarose gel electrophoresis. Results. Cytogenetic and molecular-cytogenetic investigations of SA material identified karyotype anomalies in 32.4 % of cases with prevalence of autosomal trisomy β 42.65 %, triploidy β 30.38 % and monosomy X β 19.11 %. Complex analysis of frequency and distribution of allelic variants of genes HLA-DRB1 and HLA-DQA1 allowed establishing the alleles DRB1*0301, DRB1*1101-1104 and DQA1*0501 to be aggressor alleles in women with recurrent pregnancy loss (RPL). The cumulative homology of allelic polymorphism of more than 50 % of HLA-DRB1 and HLA-DQA1 loci between partners increases the risk of RPL by almost four times. Conclusion. The detected chromosome aneuploidies in the samples from products of conception and the changes in the major histocompatibility complex genes can cause the failure of a couples reproductive function and can lead to an early fetal loss.ΠΠ΅ΡΠ°. ΠΡΡΠ°Π½ΠΎΠ²ΠΈΡΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½Ρ Π°Π½ΠΎΠΌΠ°Π»ΡΡ Ρ ΠΌΠ°ΡΠ΅ΡΡΠ°Π»Ρ ΡΠ°Π½Π½ΡΡ
ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΠΈΡ
Π²ΡΡΠ°Ρ Ρ Π°Π»Π΅Π»ΡΠ½ΠΈΠΉ ΠΏΠΎΠ»ΡΠΌΠΎΡΡΡΠ·ΠΌ Π³Π΅Π½ΡΠ² HLA β DRB1 Ρ DQA1 Ρ ΠΏΠΎΠ΄ΡΡΠΆΠ½ΡΡ
ΠΏΠ°Ρ ΡΠ· Π½Π°Π²ΠΈΠΊΠΎΠ²ΠΈΠΌ Π½Π΅Π²ΠΈΠ½ΠΎΡΡΠ²Π°Π½Π½ΡΠΌ Π²Π°Π³ΡΡΠ½ΠΎΡΡΡ. ΠΠ΅ΡΠΎΠ΄ΠΈ. Π‘ΡΠ°Π½Π΄Π°ΡΡΠ½ΠΈΠΉ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ½ΠΈΠΉ ΡΠ° ΡΠ½ΡΠ΅ΡΡΠ°Π·Π½ΠΈΠΉ mFISH ΠΌΠ΅ΡΠΎΠ΄ΠΈ, Π²ΠΈΠ΄ΡΠ»Π΅Π½Π½Ρ ΠΠΠ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π²ΠΈΡΠΎΠ»ΡΠ²Π°Π½Π½Ρ, ΠΠΠ , Π΅Π»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² Π°Π³Π°ΡΠΎΠ·Π½ΠΎΠΌΡ Π³Π΅Π»Ρ. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ. Π¦ΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ½Ρ ΡΠ° ΠΌΠΎΠ»Π΅ΠΊΡΒΠ»ΡΡΠ½ΠΎ-ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ½Ρ Π΄ΠΎΡΠ»ΡΠ΄ΠΆΠ΅Π½Ρ ΠΌΠ°ΡΠ΅ΡΡΠ°Π»Ρ Π²ΡΡΠ°ΡΠ΅Π½ΠΈΡ
Π²Π°Π³ΡΡΠ½ΠΎΡΡΠ΅ΠΉ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΡΡ ΠΊΠ°ΡΡΠΎΡΠΈΠΏΡ Π² 32.4 % Π²ΠΈΠΏΠ°Π΄ΠΊΠ°Ρ
Π· ΠΏΠ΅ΡΠ΅Π²Π°ΠΆΠ°Π½Π½ΡΠΌ Π°ΡΡΠΎΡΠΎΠΌΠ½ΠΈΡ
ΡΡΠΈΡΠΎΠΌΡΠΉ β 42.65 %, ΡΡΠΈΠΏΠ»ΠΎΡΠ΄ΡΠΉ β 30.38 % Ρ ΠΌΠΎΠ½ΠΎΡΠΎΠΌΡΡ X β 19.11 %. ΠΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΈΠΉ Π°Π½Π°Π»ΡΠ· ΡΠ°ΡΡΠΎΡΠΈ Ρ ΡΠΎΠ·ΠΏΠΎΠ΄ΡΠ»Ρ Π°Π»Π΅Π»ΡΠ½ΠΈΡ
Π²Π°ΡΡΠ°Π½ΡΡΠ² Π³Π΅Π½ΡΠ² HLA-DRB1 Ρ HLA-DQA1 Π΄ΠΎΠ·Π²ΠΎΠ»ΠΈΠ² Π²ΡΡΠ°Π½ΠΎΠ²ΠΈΡΠΈ, ΡΠΎ DRB1*0301, DRB1*1101-1104 Ρ DQA1*0501 Ρ Π°Π»Π΅Π»ΡΠΌΠΈ-Π°Π³ΡΠ΅ΡΠΎΡΠ°ΠΌΠΈ Ρ ΠΆΡΠ½ΠΎΠΊ ΡΠ· ΡΠ°Π½Π½ΡΠΌΠΈ ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΠΈΠΌΠΈ Π²ΡΡΠ°ΡΠ°ΠΌΠΈ (Π Π Π). Π‘ΡΠΊΡΠΏΠ½Π° Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΡΡ Π°Π»Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ»ΡΠΌΠΎΡΡΡΠ·ΠΌΡ Π»ΠΎΠΊΡΡΡΠ² HLA-DRB1 Ρ HLA-DQA1 Π±ΡΠ»ΡΡΠ΅ 50 % ΠΌΡΠΆ ΠΏΠ°ΡΡΠ½Π΅ΡΠ°ΠΌΠΈ Π·Π±ΡΠ»ΡΡΡΡ ΡΠΈΠ·ΠΈΠΊ Π Π Π ΠΌΠ°ΠΉΠΆΠ΅ Π² ΡΠΎΡΠΈΡΠΈ ΡΠ°Π·ΠΈ. ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½Ρ Π°Π½Π΅ΡΠΏΠ»ΠΎΡΠ΄ΡΡ Π² ΠΌΠ°ΡΠ΅ΡΡΠ°Π»Ρ Π²ΡΡΠ°ΡΠ΅Π½ΠΈΡ
Π²Π°Π³ΡΡΠ½ΠΎΡΡΠ΅ΠΉ ΡΠ° Π·ΠΌΡΠ½ΠΈ Π² Π³Π΅Π½Π°Ρ
Π³ΠΎΠ»ΠΎΠ²Π½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π³ΡΡΡΠΎΡΡΠΌΡΡΡΠ½ΠΎΡΡΡ Ρ ΠΏΠΎΠ΄ΡΡΠΆΠ½ΡΡ
ΠΏΠ°Ρ ΠΌΠΎΠΆΡΡΡ Π²ΠΈΠΊΠ»ΠΈΠΊΠ°ΡΠΈ ΠΏΠΎΡΡΡΠ΅Π½Π½Ρ ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΠΎΡ ΡΡΠ½ΠΊΡΡΡ ΡΠ° ΡΠ°Π½Π½Ρ Π΅Π»ΡΠΌΡΠ½Π°ΡΡΡ ΠΏΠ»ΠΎΠ΄Π°.Π¦Π΅Π»Ρ. ΠΈΠ·ΡΡΠΈΡΡ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΡΠ΅ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Π² Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π΅ ΡΠ°Π½Π½ΠΈΡ
ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΡΡ
ΠΏΠΎΡΠ΅ΡΡ ΠΈ Π°Π»Π»Π΅Π»ΡΠ½ΡΠΉ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌ Π³Π΅Π½ΠΎΠ² HLA β DRB1 ΠΈ DQA1 Ρ ΡΡΠΏΡΡΠΆΠ΅ΡΠΊΠΈΡ
ΠΏΠ°Ρ Ρ ΠΏΡΠΈΠ²ΡΡΠ½ΡΠΌ Π½Π΅Π²ΡΠ½Π°ΡΠΈΠ²Π°Π½ΠΈΠ΅ΠΌ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΠΈ. ΠΠ΅ΡΠΎΠ΄Ρ. ΡΡΠ°Π½ΒΠ΄Π°ΡΡΠ½ΡΠΉ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΈ ΠΈΠ½ΡΠ΅ΡΡΠ°Π·Π½ΡΠΉ mFISH ΠΌΠ΅ΡΠΎΠ΄Ρ, Π²ΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΠΠ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π²ΡΡΠ°Π»ΠΈΠ²Π°Π½ΠΈΡ, ΠΠ¦Π , ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² Π°Π³Π°ΡΠΎΠ·Π½ΠΎΠΌ Π³Π΅Π»Π΅. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠ΅ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π° ΡΠ°Π½Π½ΠΈΡ
ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΡΡ
ΠΏΠΎΡΠ΅ΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ ΠΊΠ°ΡΠΈΠΎΡΠΈΠΏΠ° Π² 32.4 % ΡΠ»ΡΡΠ°Π΅Π² Ρ ΠΏΡΠ΅ΠΎΠ±Π»Π°ΒΠ΄Π°Π½ΠΈΠ΅ΠΌ Π°ΡΡΠΎΡΠΎΠΌΠ½ΡΡ
ΡΡΠΈΡΠΎΠΌΠΈΠΉ β 42.65 %, ΡΡΠΈΠΏΠ»ΠΎΠΈΠ΄ΠΈΠΉ β 30.38 % ΠΈ ΠΌΠΎΠ½ΠΎΡΠΎΠΌΠΈΠΈ Π₯ β 19.11 %. ΠΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΡΡΠΎΡΡ ΠΈ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π°Π»Π»Π΅Π»ΡΠ½ΡΡ
Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² Π³Π΅Π½ΠΎΠ² HLA-DRB1 ΠΈ HLA-DQA1ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ DRB1*0301, DRB1*1101-1104 ΠΈ DQA1*0501 ΡΠ²Π»ΡΡΡΡΡ Π°Π»Π»Π΅Π»ΡΠΌΠΈ-Π°Π³ΡΠ΅ΡΡΠΎΡΠ°ΠΌΠΈ Ρ ΠΆΠ΅Π½ΡΠΈΠ½ Ρ ΡΠ°Π½Π½ΠΈΠΌΠΈ ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΡΠΌΠΈ ΠΏΠΎΡΠ΅ΡΡΠΌΠΈ (Π Π Π). Π‘ΠΎΠ²ΠΎΠΊΡΠΏΠ½Π°Ρ Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΡ Π°Π»Π»Π΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠΈΠ·ΠΌΠ° Π»ΠΎΠΊΡΡΠΎΠ² HLA-DRB1 ΠΈ HLA-DQA1 Π±ΠΎΠ»Π΅Π΅ 50 % ΠΌΠ΅ΠΆΠ΄Ρ ΠΏΠ°ΡΡΠ½Π΅ΡΠ°ΠΌΠΈ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅Ρ ΡΠΈΡΠΊ Π Π Π ΠΏΠΎΡΡΠΈ Π² ΡΠ΅ΡΡΡΠ΅ ΡΠ°Π·Π°. ΠΡΠ²ΠΎΠ΄Ρ. ΠΡΡΠ²Π»Π΅Π½Π½ΡΠ΅ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΠ½ΡΠ΅ Π°Π½Π΅ΡΠΏΠ»ΠΎΠΈΠ΄ΠΈΠΈ Π² ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Π΅ ΡΠ°ΠΌΠΎΠΏΡΠΎΠΈΠ·Π²ΠΎΠ»ΡΠ½ΡΡ
Π²ΡΠΊΠΈΠ΄ΡΡΠ΅ΠΉ ΠΈ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Π² Π³Π΅Π½Π°Ρ
Π³Π»Π°Π²Π½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π³ΠΈΡΡΠΎΡΠΎΠ²ΠΌΠ΅ΡΡΠΈΠΌΠΎΡΡΠΈ Ρ ΡΡΠΏΡΡΠΆΠ΅ΡΠΊΠΈΡ
ΠΏΠ°Ρ ΠΌΠΎΠ³ΡΡ Π²ΡΠ·ΡΠ²Π°ΡΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΏΡΠΎΠ΄ΡΠΊΡΠΈΠ²Π½ΠΎΠΉ ΡΡΠ½ΠΊΡΠΈΠΈ ΠΈ ΡΠ»ΠΈΠΌΠΈΠ½Π°ΡΠΈΡ ΠΏΠ»ΠΎΠ΄Π° Π² ΡΠ°Π½Π½Π΅ΠΌ ΠΏΠ΅ΡΠΈΠΎΠ΄Π΅ Π±Π΅ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΡΡΠΈ
INHERITED 15Q DUPLICATION IN THREE NOT RELATED UKRAINIAN FAMILIES
Background. 15q duplication syndrome (Dup15q) is caused by the presence of an extra maternally derived copy of the Prader-Willi/Angelman critical region (PWACR) within chromosome 15q11.2-q13.1. The syndrome is clinically identifiable and characterized by intellectual disability, hypotonia, motor delays, autism spectrum disorder, epilepsy, and behavioral difficulties [1, 12]. The prevalence of Dup15q in the general population is unknown but may be as high as 1:5000 [10]. The syndrome most commonly occurs in one of two forms: an extra isodicentric 15 chromosome or an interstitial duplication [4]. Most reported cases concern de novo mutation.
Aim. To highlight the importance of genetic testing in patients with neurodevelopmental disorders and emphasizes the need for further research to understand the underlying genetic mechanisms of Dup15q depending on the origin of the inherited duplication.
Materials and methods. The study used next-generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), and karyotype analysis to confirm the interstitial duplication.
Results. We present the phenotype description and diagnostic prospects of three patients from different families who inherited interstitial 15q duplication from a phenotypically healthy mother. The patients exhibited symptoms consistent with Dup15q, including intellectual disability, delayed speech, difficulty understanding spoken language, hyperactivity, epilepsy and sleep disorders.
Conclusion. The inherited interstitial duplication 15q is phenotypical presented only in case of maternal origin and vary in clinical presentation. We suggest as the first choice MLPA method as most cost and time effective in cases of Dup15q suspicion
Familial Infertility (Azoospermia and Cryptozoospermia) in Two BrothersβCarriers of t(1;7) Complex Chromosomal Rearrangement (CCR): Β Molecular Cytogenetic Analysis
Structural aberrations involving more than two breakpoints on two or more chromosomes are known as complex chromosomal rearrangements (CCRs). They can reduce fertility through gametogenesis arrest developed due to disrupted chromosomal pairing in the pachytene stage. We present a familial case of two infertile brothers (with azoospermia and cryptozoospermia) and their mother, carriers of an exceptional type of CCR involving chromosomes 1 and 7 and three breakpoints. The aim was to identify whether meiotic disruption was caused by CCR and/or genomic mutations. Additionally, we performed a literature survey for male CCR carriers with reproductive failures. The characterization of the CCR chromosomes and potential genomic aberrations was performed using: G-banding using trypsin and Giemsa staining (GTG banding), fluorescent in situ hybridization (FISH) (including multicolor FISH (mFISH) and bacterial artificial chromosome (BAC)-FISH), and genome-wide array comparative genomic hybridization (aCGH). The CCR description was established as: der(1)(1qter->1q42.3::1p21->1q42.3::7p14.3->7pter), der(7)(1pter->1p2 1::7p14.3->7qter). aCGH revealed three rare genes variants: ASMT, GARNL3, and SESTD1, which were ruled out due to unlikely biological functions. The aCGH analysis of three breakpoint CCR regions did not reveal copy number variations (CNVs) with biologically plausible genes. Synaptonemal complex evaluation (brother-1; spermatocytes II/oligobiopsy; the silver staining technique) showed incomplete conjugation of the chromosomes. Associations between CCR and the sex chromosomes (by FISH) were not found. A meiotic segregation pattern (brother-2; ejaculated spermatozoa; FISH) revealed 29.21% genetically normal/balanced spermatozoa. The aCGH analysis could not detect smaller intergenic CNVs of few kb or smaller (indels of single exons or few nucleotides). Since chromosomal aberrations frequently do not affect the phenotype of the carrier, in contrast to the negative influence on spermatogenesis, there is an obvious need for genomic sequencing to investigate the point mutations that may be responsible for the differences between the azoospermic and cryptozoospermic phenotypes observed in a family. Progeny from the same parents provide a unique opportunity to discover a novel genomic background of male infertility
Complex cytogenetic and molecular-genetic analysis of males with spermatogenesis failure
The chromosomal anomalies, microdeletions of AZF region of Y-chromosome and CFTR gene mutations have been studied among 80 infertile men with idiopathic spermatogenetic failure: 36 (45 %) patients with aspermia, 19 (24 %) patients with azoospermia and 25 (31 %) patients with severe oligoasthenoteratozoospermia. In total 30 % males with spermatogenetic failure genetic factor of infertility was observed. Karyotype anomalies were observed in 17.5 % of infertile men, within 16.2 % numerical and structural gonosomal anomalies and in 1.3 % β Robertsonian translocation were revealed. In 11 % males with spermatogenetic failure, Y-chromosome AZF region microdeletions were detected. The frequency of CFTR major mutation F508del among infertile men was 6.25 %. 5T allele of polymorphic locus IVS8polyT was detected in 7.5 % of examined men. The results obtained indicate the high complexity of cytogenetic and moleculargenetic studies of male infertility.ΠΠ·ΡΡΠ°Π»ΠΈ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ, ΠΌΠΈΠΊΡΠΎΠ΄Π΅Π»Π΅ΡΠΈΠΈ AZF ΡΠ΅Π³ΠΈΠΎΠ½Π° Y-Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ ΠΈ ΠΌΡΡΠ°ΡΠΈΠΈ Π³Π΅Π½Π° Π’Π ΠΠ Ρ 80 ΠΌΡΠΆΡΠΈΠ½ Ρ ΠΈΠ΄ΠΈΠΎΠΏΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π°, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ: Ρ 36 (45 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π°ΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ, 19 (24 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π°Π·ΠΎΠΎΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ ΠΈ 25 (31 %) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΎΠ»ΠΈΠ³ΠΎΠ°ΡΡΠ΅Π½ΠΎΡΠ΅ΡΠ°ΡΠΎΠ·ΠΎΠΎΡΠΏΠ΅ΡΠΌΠΈΠ΅ΠΉ IV ΡΡΠ΅ΠΏΠ΅Π½ΠΈ. Π ΠΎΠ±ΡΠ΅ΠΌ Ρ 30 % ΠΌΡΠΆΡΠΈΠ½ Ρ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π° ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Ρ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΠ°ΠΊΡΠΎΡΡ Π±Π΅ΡΠΏΠ»ΠΎΠ΄ΠΈΡ. ΠΠ°ΡΡΡΠ΅Π½ΠΈΡ ΠΊΠ°ΡΠΈΠΎΡΠΈΠΏΠ° Π½Π°Π±Π»ΡΠ΄Π°Π»ΠΈ Ρ 17.5 % Π±Π΅ΡΠΏΠ»ΠΎΠ΄Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½, ΡΡΠ΅Π΄ΠΈ Π½ΠΈΡ
Ρ 16.2 % β ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΠ΅ ΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΡΠ΅ Π°Π½ΠΎΠΌΠ°Π»ΠΈΠΈ Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌ ΠΈ Ρ 1.3 % β ΡΠΎΠ±Π΅ΡΡΡΠΎΠ½ΠΎΠ²ΡΠΊΡΡ ΡΡΠ°Π½ΡΠ»ΠΎΠΊΠ°ΡΠΈΡ. Π£ 11 % ΠΌΡΠΆΡΠΈΠ½ Ρ Π½Π°ΡΡΡΠ΅Π½ΠΈΡΠΌΠΈ ΡΠΏΠ΅ΡΠΌΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π° Π²ΡΡΠ²ΠΈΠ»ΠΈ ΠΌΠΈΠΊΡΠΎΠ΄Π΅Π»Π΅ΡΠΈΠΈ AZF ΡΠ΅Π³ΠΈΠΎΠ½Π° Y Ρ
ΡΠΎΠΌΠΎΡΠΎΠΌΡ. Π§Π°ΡΡΠΎΡΠ° ΠΌΠ°ΠΆΠΎΡΠ½ΠΎΠΉ ΠΌΡΡΠ°ΡΠΈΠΈ F508del Π³Π΅Π½Π° Π’Π ΠΠ ΡΡΠ΅Π΄ΠΈ Π±Π΅ΡΠΏΠ»ΠΎΠ΄Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½ ΡΠΎΡΡΠ°Π²ΠΈΠ»Π° 6.25 %. 5T Π°Π»Π»Π΅Π»Ρ ΠΏΠΎΠ»ΠΈΠΌΠΎΡΡΠ½ΠΎΠ³ΠΎ Π»ΠΎΠΊΡΡΠ° IVS8polyT Π²ΡΡΠ²ΠΈΠ»ΠΈ Ρ 7.5 % ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΡΠΆΡΠΈΠ½. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡΡ ΠΎ Π²ΡΡΠΎΠΊΠΎΠΉ ΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠ³ΠΎ ΡΠΈΡΠΎΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ ΠΌΡΠΆΡΠΊΠΎΠΌ Π±Π΅ΡΠΏΠ»ΠΎΠ΄ΠΈΠΈ