A Rare Combination of 45,x/46,xy Mosaicism and Y Chromosome Microdeletion in an Infertile Man with Azoospermia

Infertility is observed 15% of married couples. It has been shown that almost 30-50% of the infertility is originating from male (4,6). One of the major reasons for male infertility is chromosomal abnormalities, which varies between 2% and 88% in literature, and it is higher in infertile cases than it is in normal population (3,4). Especially in cases with azoospermia, the frequency of cytogenetic abnormalities is about 15% (7,8).45,X/46,XY mosaicism is a rare chromosomal abnormality. This abnormality arise phenotypical variation and, with sexual infantilism findings, it leads to various phenotypes such as indefinite genitals, male with hypospadias and male with azoospermia (1,2,10). The microdeletions of genes located in long arms of the Y chromosome and required for fertility (azoospermia factor, AZF) are the important reasons for male infertility. These AZF microdeletions that cannot be detected cytogenetically are identified in 3 regions of Y chromosome (AZFa, AZFb, and AZFc). These microdeletions can cause azoospermia or oligospermia, and the most frequent one is AZFc region microdeletion (9,11 ).In this report, we present a rare combination of 45,X/46,XY mosaicism and Y chromosome microdeletion in an infertile man with azoospermia. A twenty-eight-year-old male patient was suffered from infertility for eight years. Hormonal assessment of the patient was normal range. In the physical examination of the patient, it has been observed that he had normal male phenotype, which both of his testicles were normal, and the vas deferens were palpable bilaterally.The patient was found azoospermia in the semen analysis. Chromosome analysis and Y chromosome microdeletion analysis were performed for the patient. According to the analysis of metaphase chromosomes, 45,X[41 ]/46,X,del(Y)(q 11 )[9] karyotype was detected in the patient (Fig. 1 ). As a result of CBG banding performed to the patient found to have 45,XM 6,XY mosaicism and deletion in qll region of Y chromosome, no heterochromatin region was detected in relation to Y chromosome. In order to confirm the mosaicism and deletion findings, FISH method was utilized, and it was detected in 15% of examined cells that no signal was received from Yql2 region, while the signal was received from X chromosome centromere and SRY region. In 85% of examined cells, X chromosome was observed as a single signal (Fig. 2).After DNA isolation from the peripheral blood samples with EDTA taken for Y microdeletion analysis, by using appropriate Sequence-Tagged Sites, microdeletion was scanned using multiplex polymerase chain reaction. As a result of the analysis, microdeletions were detected in Y chromosome's AZFb (sY 127, sY 134) and AZFc (sY 254, sY 255) regions. Moreover, in scrotal Color Doppler USG, abdominal USG and echocardiography results of the patient, no pathological finding was detected.Azoospermia is observed in 1% of all of the males and 15% of infertile males. Again, in cases with azoospermia, the frequency of genetic anomaly is higher than normal population. About the genetic reasons for male infertility, the karyotypical defects, Y microdeletions, and gene mutations should be taken into consideration. Especially Y chromosome is required for germ cell development (10,11). Telvi et al. ( 12) have reported that no relation has been determined between 45,X cell ratios and masculinization in males with 45,X/46,XY mosaicism. Moreover, they have reported that detection of 45,X cells in blood or gonads is independent from masculinization characteristics.In the literature that 45,X/46,XY mosaicism is related to Y chromosome anomalies. Y chromosome structural anomalies generally accompany with 45,X cell line, and 45,X cell line is thought to emerge with the loss of Y chromosome with impairment of structure and stability. This arises the phenotypic variation, and various phenotypes may be seen such as female phenotype, indefinite genitals, male with hypospadias and male with azoospermia (1, 10, 12). …