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Case Report |
From the Department of Reproduction and Genetics, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, Peoples' Republic of China.
| Correspondence to: Ying-Xia Cui, Department of Reproduction and Genetics, Jinling Hospital, Clinical School of Nanjing University, 305 East Zhongshan Road, Nanjing 210002, P.R. China (e-mail: cyx5510{at}hotmail.com). |
| Received for publication September 25, 2006; accepted for publication December 26, 2006. |
Case Report
A 30-year-old man attended our center because of an 8-year history of
infertility. Physical examination revealed the following: height 168 cm,
weight 60 kg, normal male external genitalia, slightly soft and markedly small
testes (6 mL bilaterally vs 19.8 ± 7.1 mL for normal adult Chinese).
Semen analysis according to WHO guidelines showed no sperm in any of 3 routine
tests. Serum hormonal profile was normal for T, E2, luteinizing hormone, and
prolactin and high for follicle-stimulating hormone (27 IU/L vs 5–20.0
IU/L for normal adult Chinese). His intelligence and development were normal.
After obtaining patient approval, testicular biopsy was performed, and the
pathological result showed the presence of only Sertoli cells and absence of
germ cells in all examined seminiferous tubules. No ovarian tissue was found
(Figure 1). The Ethics
Committee of Jinling Hospital approved this research.
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Results
The karyotype 45,X/46,Xdel(Y)/47,Xdel(Y) del(Y) was observed in the
lymphocytes of peripheral blood at a ratio of 27:68:5
(Figure 2A through C). The
result of FISH was consistent with that of cytogenetics. The breakpoint of the
deleted Y chromosome was located at q11, and the C-band showed the loss of the
heterochromatin region (Figure
2D). Multiplex PCR showed the presence of AZFa (sY86, sY84) and
the absence of AZFb (sY127, sY134) and AZFc (sY254, sY255). The results of
simple PCR showed positive sY87 and sY88, whereas sY95, sY105, sY117, and
sY160 were negative (data not shown). The breakpoint was between sY88 and sY95
(Figure 3A and B). Taken
together, these data showed that the deleted segment was from interval 5H to
qter, and the karyotype was 45,X/46,Xdel(Y)(q11.23)/47,Xdel(Y)(q11.23)
del(Y)(q11.23). Both parental chromosomes were normal. Multiplex PCR results
of the father and the normal fertile man showed presence of all loci
tested.
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Discussion
The predominant karyotype in this male with 46,Xdel(Y) coexisting with 45,X
and 47,Xdel(Y) del(Y) cell lines suggested that the de novo independent events
were involved in the processes of meiosis and mitosis, respectively. First,
the deleted Y chromosome was proposed to arise by a break event of the Yq11
region, followed by the loss of a fragment without a centromere during the
paternal meiosis stage. Second, the deleted Y chromosomal nondisjunction event
occurred in the postzygotic mitosis stage. The karyotype
45,X/46,Xdel(Y)/47,Xdel(Y) del(Y) was reported for the first time. The
mechanism causing the nondisjunction is poorly understood. We suggested a
hypothesis that the genes in AZFb and AZFc were not only associated with
spermatogenesis but also with Y chromosomal stability. Y chromosomal loss or
its nondisjunction might further aggravate the failure of spermatogenesis.
Patients with a karyotype 45,X/46,Xdel(Y)(q11) can present a wide spectrum of sex phenotypes, including complete masculinization, ambiguous genitalia, or Turner syndrome (Robinson et al, 1999; Papadimas et al, 2001; Werner et al, 2005). These phenotypic differences are related not only to the presence or absence of the SRY gene on Yp, but also to the proportion of 45,X line in gonadal tissue. As is known, a sufficient SRY transcript level is necessary to trigger testes formation. Once testes differentiate, male endocrine function is responsible for the rest of the events involving male phenotypic sexual differentiation. However, if the 45,X line was predominant in gonadal tissue, the phenotype of Turner syndrome would appear. Our patient showed a higher percentage of 45,X cell line (27%) in the peripheral blood, but we speculate that the proportion in gonadal tissue is lower than that in the blood. This is supported by the patient's normal male phenotype.
The case is associated with deletions of sY117 and sY127 for RBMY1 in the AZFb region with the loss of sY254 and sY255 for DAZ in theAZFc region. Thesegenedeletions should be responsible for the failure of spermatogenesis and male infertility. On the basis of the testicular pathologic pattern with Sertoli cell–only syndrome, the partner of the patient should be inseminated with donor sperm.
We offered an example of del(Y) associated with nondisjunction during mitosis division, which has not been reported previously.
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) indicates Sertoli cells. The arrow (
) indicates Leydig cells.
Scale bar = 40 µm.
