Clinical and molecular cytogenetic studies in three infertile patients with mosaic rearranged Y chromosomes

Abstract

Isodicentrics (idic) are structural anomalies of the Y chromosome associated with a 45,X cell line and a broad spectrum of phenotypes. We characterized the rearranged Y chromosomes from three azoospermic males by fluorescence in-situ hybridization (FISH) and PCR. Chromosome study was performed on lymphocytes and testicular biopsy. FISH analysis and PCR established the degree of mosaicism and analysed specific Y regions. Two patients showed a 45,X/46,X,?idic(Y) karyotype with varying degrees of mosaicism. FISH demonstrated the presence of two centromeres and two SRY regions. In the lymphocytes of the third patient, the presence of a small Y-derived marker was also observed. An additional cell line with two idic(Y) was present in the testicular biopsy of the same patient. PCR showed the breakpoint between SY182 (KALY) and SY121 in Yq11.221-q11.222 region in all the cases. For the evaluation of the mosaicism, different tissues must be investigated. The phenotypical sex depends more on the number of copies of the SRY gene rather than on the percentage of 45,X cells, at least in the gonads. The combined use of classical and molecular cytogenetics is necessary for delineating the chromosome regions involved allowing a better genotype-phenotype correlation.

A Rare Cause of Male Infertility: 45,X/46,XY Mosaicism

“…However, short stature is not a consistent finding in all 45,X/46,XY individuals. Some cases had normal stature in our series and this result was similar to several previous reports [4, 9, 10]. This situation may be associated with normal testosterone levels.…”

Phenotypic spectrum of 45,X/46,XY males with a ring Y chromosome and bilaterally descended testes

“…Although less clear in 45,X/46,XY males with bilaterally descended testes, phenotypic 45,X females (regardless of mosaicism) have an increased risk of congenital anomalies, Down syndrome, fetal wastage, and 45,X offspring (15). Bettio et al (16) described three infertile males with 45,X/46,X,idic(Yq11), normal height (171,163, and 170 cm respectively), azoospermia, elevated gonadotropins in two patients, normal LH and testosterone in one patient. The normal stature in all three patients may be related to the presence of three copies of the statural determining gene SHOX in the isodicentric Y cells.…”

Chromosome Y Isodicentrics in two Cases with Ambiguous genitalia and Features of Turner Syndrome

“…Abnormalities in the number or the structure of sex chromosomes are sometimes associated with a wide spectrum of phenotypes, ranging from almost male through mixed gonadal dysgenesis to female with Turner syndrome [1]. The most common structural abnormalities of the human Y chromosome are dicentrics [1].…”

“…Abnormalities in the number or the structure of sex chromosomes are sometimes associated with a wide spectrum of phenotypes, ranging from almost male through mixed gonadal dysgenesis to female with Turner syndrome [1]. The most common structural abnormalities of the human Y chromosome are dicentrics [1]. Patients with ambiguous genitalia and patients with Turner syndrome, beside a 45,X cell line, frequently have an additional one that contains structural abnormalities of the Y chromosome [2][3][4].…”