Structural abnormalities of the Y chromosome and abnormal external genitals

Summary Three infants with different types of Y-chromosome abnomalies, including short- and/or long-arm deletion and mosaicism, are reported. The karyotypes of these patients were: 45,X/46,X,del(Y)/47,X,del(Y), del(Y) on peripheral lymphocytes and 45,X/46,X, del(Y) on gonadal tissue (case 1), 45,X/46,X,del(Y) (case 2), and 45,X/46,X,r(Y) (case 3). In case 1 the euchromatic segment on the deleted Y was distinctly larger than that of the father's Y.The three infants had no gross phenotypic anomalies except ambiguous genitals and low birth weight, and they were small for date. The histologic diagnosis in two of them was mixed gonodal dysgenesis (cases 1 and 2).The relationship between structural abnormalities of the Y chromosome and ambiguous genitals as well as male-determining factors is discussed.     

Genetic drift of marker Y chromosome del(Y)(q12) in Khanty from the lower Ob river

Summary A cytogenetic study of Khanty from the lower Ob river in West Siberia has detected a high frequency of the Y chromosome heterochromatin subtotal deletion—del(Y) (q12). This morphologically identical deletion was found in 32 of 154 males examined (20.8%). The carriers had 10 different surnames. Taking into account the small size, isolation by distance, and historical pecularities of the surname formation of the population, it has been concluded that the high frequency of the del(Y)(q12) results from the genetic drift of the marker chromosome.     

无精子症和严重少精子症患者Y染色体微缺失研究

目的：研究Y染色体微缺失与男性不育的关系。方法：采用多重PCR技术,研究正常男性、无精子症和严重少精子症男性不育患者Y染色体无精子因子（AZF）区域3个序列标志位点（STS）的缺失情况。结果：在93例无精子症或严重少精子症患者中,15例有Y染色体微缺失,缺失率为16%。其中,42例无精子症患者中,6例为AZFc区SY255位点缺失,2例为AZFb区SY134位点缺失;51例严重少精子症患者中,7例为AZFc区SY255位点缺失。40例正常男性无Y染色体微缺失。结论：多重PCR技术是简便而有效的对男性不育患者进行Y染色体微缺失筛查的方法;Y染色体微缺失是造成男性不育的一个重要原因,对男性不育患者进行辅助生育技术治疗前应常规进行Y染色体微缺失的检测。     

Types of Y chromosome deletions and their frequency in infertile men

Deletions of Y chromosome AZF locus were analyzed during a large-scale andrological and genetic examination of 810 infertile men. The search for Yq microdeletions was carried out according to the standard EAA/EMQN guidelines. The breakpoints were mapped for the deletions in AZF locus. The Y chromosome macro- and microdeletions were detected in 61 (7.5%) infertile men. The frequencies of AZF deletions during azoospermia and severe oligozoospermia amounted to 12.2 and 8.1 %, respectively. On the whole, the frequencies of Yq microdeletions and the genophenotypic correlations characteristic of various AZF deletion types comply with the relevant published data. However, spermatozoids in the ejaculate sediment of men with completely deleted AZFa region or AZFb+c deletions (from solitary spermatozoids to several dozens) were detected for the first time. It was demonstrated that the breakpoints were localized between AZFa and AZFb regions proximally to AZFb+c microdeletions for the majority of cytogenetically detectable deletions in the Y chromosome long arm. This indicates that the mechanisms underlying Yq macro- and microdeletions are somewhat different. The issues related to the role of Y chromosome deletions in the origins of monosomy for X chromosome and X/XY mosaicism are discussed.     

Types of Y chromosome deletions and their frequency in infertile men

Y chromosome deletions in the AZF locus were analyzed during a large-scale andrological and genetic examination of 810 infertile men. The search for Yq microdeletions was carried out according to the standard EAA/EMQN guidelines. The breakpoints were mapped for the revealed AZF deletions. The Y chromosome macro-and microdeletions were detected in 61 (7.5%) infertile men. The frequencies of AZF deletions in patients with azoospermia and severe oligozoospermia amounted to 12.2 and 8.1%, respectively. On the whole, the frequencies of Yq microdeletions and the genophenotypic correlations characteristic of various AZF deletion types agree with the relevant published data. However, spermatozoa in the ejaculate sediment of men with completely deleted AZFa region or AZFb+c deletions (from solitary spermatozoa to several dozens) were detected for the first time. It was demonstrated that the breakpoints were localized between AZFa and AZFb regions proximally to AZFb+c microdeletions for the majority of cytogenetically detectable deletions of the Y chromosome long arm. This indicates that the mechanisms underlying Yq macro-and microdeletions are somewhat different. The issues related to the role of Y chromosome deletions in the origins of X chromosome monosomy and X/XY mosaicism are discussed.     

Deletion - translocation del (12) (p11) leads to (t10;12) (p13;pII).

Renewed examinatinon with improved banding techniques of a boy previously reported to have the karyotype 46, XY,del(12)(p11) revealed a translocation 46, XY,t(10;12)(p13;p11), and reexamination of a boy previously reported to have the karyotype 46,XY/46,XY,del(5)(p13) showed the same mosaicism, but with a significantly lower frequency of cells with del(5)(p13), 8% compared with 23% at the time of birth. The decrease of the frequency of cells with chromosome abnormality in mixoploids during the first years of life as found in the present case as well as in prevously reported cases is discussed.     

Clinical consequences of a human non-fluorescent Y chromosome (Ynf)

A new case of ambiguous genitalia and immature tissue in the left gonad is presented. Cytogenetic findings with various techniques demonstrated that the distal two-thirds of the long arm of the Y chromosome is deleted. Q-banding showed a non-fluorescent Y; three positive bands were however noted when the DA/DAPI technique was applied. After a review of the literature, it was concluded that the non-fluorescent Y chromosome (Ynf) when inherited from generation to generation is a heteromorphism in normal males. However, in our case, where the proband's Y is lacking the fluorescent segment, a simple deletion does not appear to adequately explain the DA/DAPI positive bands. Possibly, a deletion followed by a structural rearrangement of the non-fluorescent segment had occurred de novo. The highly Y-specific DNA sequences present in the fluorescent segment are absent in these patients. The abnormal development in these cases is due to the presence of the 45,X cell line. The gene responsible for spermatogenesis has been localized to the non-fluorescent region in the long arm of the Y chromosome. Furthermore, it is concluded that two types of non-fluorescent Y chromosomes can be found in the population; one is a normal inherent heteromorphic variant, while the other appears to be an abnormality, especially in cases with azoospermia. Such distinctions should clearly be established prior to genetic counseling for patients with so called Ynf or del (Yd).     

X/Y translocation in a family with Leri-Weill dyschondrosteosis

An X/Y translocation associated with Leri-Weill dyschondrosteosis (LWD) was detected in a boy and in his mother. FISH analysis with specific probes for SHOX and SRY displayed no signal on the der(X), while one signal for SHOX was detected on the normal X chromosome in the mother, and one signal each for SHOX and SRY was detected on the normal Y chromosome in the proband.     

XO/XY mosaicism and non-fluorescing Y chromosome in a male

Summary An adult male of short stature and with underdeveloped external genitalia is described, who carried out a number of sexual assaults on young women. He proved to have XO/XY mosaicism and a non-fluorescing Y chromosome. It was considered to be a terminal deletion on morphological grounds. It is suggested, on the evidence of the small number of XO/XY mosaics examined by appropriate staining methods, that an abnormal Y chromosome, whether terminally deleted or non-fluorescing owing to an altered chemical state, predisposes to anaphase lagging and non-disjunction.Of eleven reported cases of XO/XY mosaicism with a non-fluorescing Y chromosome, this is the fifth of male phenotype. The severe behaviour disturbance of early onset is considered to be probably causally associated with the chromosome anomaly.     

True vs. false inv(Y)(p11q11.2): a familial instance concurrent with trisomy 21

A boy with Down syndrome due to a free trisomy 21 also had a metacentric Y chromosome with an arm euchromatic and the other heterochromatic inherited from his phenotypically normal father. This chromosome was mitotically stable and hybridized with the DYZ3 probe precisely at its primary constriction; in addition, a subtelomeric Xp/Yp probe gave the expected signal near the end of the euchromatic arm. So, the proband's karyotype was 47,X,inv(Y)(p11q11.2),+21. Given the high frequency of both chromosome anomalies, we regard its concurrence as a mere coincidence. This observation, along with previous reports, allows us to classify the apparent pericentric inversions of the Y chromosome into two types: "true" inversions characterized by an alphoid single centromere and mitotic stability, and "false" inversions in which a nonalphoid centromere has taken over the usual alphoid centromere; indeed, these chromosomes are dicentric and mitotically unstable. Finally, the inv(Y) polymorphism in man compares with that documented in other mammal species, in which the rearranged Y chromosome neither impairs the fertility nor has other phenotypical consequences.     

中国无精症、严重寡精症患者的染色体异常和Y染色体微缺失

染色体异常和Y染色体微缺失被认为是两个白种人群中常见的生精障碍相关遗传因素。为了解中国无精症、严重寡精症患者中的染色体异常和Y染色体微缺失,运用染色体G显带技术,在358个原发无精症（256人）和严重寡精症（102人）不育患者中进行染色体核型分析;同时运用多重PCR技术,在核型正常的患者和100个正常生育男性中,对Y染色体AZF区微缺失进行筛查。在358个患者中,39人（10．9％）发现有染色体异常,Klinefelter（47,XYY）最为常见。无精症患者性染色体异常频率明显高于严重寡精症患者（12．1％VS1％）。在319个核型正常的患者中,46（14．4％）发现有AZF区微缺失,无精症和寡精症患者中Y染色体微缺失频率分别为15％和13．1％,AZFc区的微缺失最为常见,AZFa区的微缺失只见于无精症患者,正常生育男性中未发现AZF区的微缺失。结果显示,在中国无精症、严重寡精症患者中,大约25％的患者有染色体异常或Y染色体AZF区微缺失,提示这两种遗传异常是中国人群生精障碍的重要相关遗传病因,有必要在男性不育的诊断以及利用细胞浆内精子注射技术进行辅助生育时,对患者的这些遗传异常进行筛查。     

46,XX, der(15),t(Y;15)(q12;p11) karyotype in an azoospermic male

We report on a Yq/15p translocation in a 23-year-old infertile male referred for Klinefelter Syndrome testing, who had azoospermia and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Conventional cytogenetic procedures giemsa trypsin giemsa (GTG) and high resolution banding (HRB) and molecular cytogenetic techniques Fluorescence In Situ Hybridization (FISH) performed on high-resolution lymphocyte chromosomes revealed the karyotype 46,XX, t(Y;15)(q12;p11). SRY-gene was confirmed to be present by classical Polymerase Chain Reaction (PCR) methods. His father carried de novo derivative chromosome 15 [45,X, t(Y;15)(q12;p11)] and was fertile; the karyotype of the father using G-band technique confirmed a reciprocal balanced translocation between chromosome Y and 15. In the proband, the der (15) has been inherited from the father because the mother had a normal karyotype (46,XX). In the proband, the der (15) could have produced genetic imbalance leading to unbalanced robertson translocation between chromosome Y and 15, which might have resulted in azoospermia and infertility in the proband. The paternal translocation might have lead to formation of imbalanced ova, which might be resulted infertility in the proband. Sister''s karyotypes was normal (46,XX) while his brother was not analyzed.     

A 45,X male with Y-specific DNA translocated onto chromosome 15.

A 20-year-old male patient with chromosomal constitution 45,X, testes and normal external genitalia was examined. Neither mosaicism nor a structurally aberrant Y chromosome was observed when routine cytogenetic analysis was performed on both lymphocytes and skin fibroblasts. Y chromosome-specific single-copy and repeated DNA sequences were detected in the patient's genome by means of 11 different recombinant-DNA probes of known regional assignment on the human Y chromosome. Data indicated that the short arm, the centromere, and part of the long-arm euchromatin of the Y chromosome have been retained and that the patient lacks deletion intervals 6 and 7 of Yq. High-resolution analysis of prometaphase chromosomes revealed additional euchromatic material on the short arm of one of the patient's chromosomes 15. After in situ hybridization with the Y chromosome-specific probe pDP105, a significant grain accumulation was observed distal to 15p11.2, suggesting a Y/15 chromosomal translocation. We conclude that some 45,X males originate from Y-chromosome/autosome translocations following a break in the proximal long arm of the Y chromosome.     

Chromosomal Abnormality and Y Chromosome Microdeletion in Chinese Patients with Azoospermia or Severe Oligozoo-spermia

Chromosomal abnormality and Y chromosome microdeletion are regarded as two frequent genetic causes associated with spermatogenic failure in Caucasian population. To investigate the distribution of the two genetic defects in Chinese patients with azoospermia or severe oligozoospermia, karyotype analysis by G-banding was carried out in 358 idiopathic infertile men, including 256 patients with azoospermia and 102 patients with severe oligozoospermia, and screening of AZF region microdeletion of Y chromosome by multiplex PCR was performed in those patients without detectable chromosomal abnormality and 100 fertile controls. Of 358 patients, 39(10.9%) were found to have chromosomal abnormalities in which Klinefelters syndrome (47, XXY) was the most common chromosomal aberration. The incidence of sex chromosomal abnormality in patients with azoospermia was significantly higher than that in patients with severe oligozoospermia (12.1% vs 1%). Among the rest of the 319 patients with normal karyotype, 46 (14.4%) were found to have microdeletions in AZF region. The prevalence rates of AZF microdeletion was 15% and 13.1% in patients with azoospermia and severe oligozoospermia respectively. The microdeletion in AZFc was the most frequent deletion and all the microdeletions in AZFa were found in azoospermic patients. No microdeletion in AZF region was detected in fertile controls. In conclusion, chromosomal abnormality and AZF region microdeletion of Y chromosome might account for about 25% of Chinese infertile patients with azoospermia or severe oligozoospermia, suggesting the two abnormalities are important genetic etiology of spematogenic failure in Chinese population and it is essential to screen them during diagnosis of male infertility before in vitro assisted fertilization by introcytoplasmic sperm injection.     

Two dicentric Y isochromosomes,one without the Yqh heterochromatic segment

Summary Two women with primary amenorrhoea and few other stigmata of Turner's syndrome were found to be chromosome mosaics: 45,X/46,X,idic(Y). In Case 1, the dicentric isochromosome Y was found to have a long-arm breakpoint of formation. This structure was interpreted as containing two Y short arms and centromeres separated by a region derived from the proximal Y long arm. One of the centromeres in the Case 1 —idic(Y) was suppressed in 80% of cells in blood, and in these cells it appeared as a regular Y-shaped chromosome. In Case 2 the idic(Y) was derived by a short-arm breakpoint of formation. In all the dicentrics of this case with one primary constriction (functional monocentrics) there was a single Cd band. In the 10% of dicentrics with two primary constrictions, there were two Cd bands. It is argued that the instability of sex isochromosomes is due to this functional dicentricity in some cells. These cases are compared with 42 other Y isochromosomes with various short- and long-arm breakpoints of formation. It is suggested that some of the nonheterochromatic, nonfluorescent Y chromosomes previously reported may be explained as dicentric i(Y) with proximal long-arm breakpoints of formation and one suppressed centromere.     

Identification of a case of Y:18 translocation using a Y-specific repetitive DNA probe

Summary We have used a recombinant DNA clone derived from the Y-specific 3,4-kb repeats for in situ chromosome hybridization and Southern blotting analysis to identify a case of de novo Y;18 translocation. The proband has a chromosome complement of 46,XY and a variant chromosome 18 with a Q-bright and C-positive short arm. The father has a normal male karyotype of 46,XY. The mother has a female karyotype of 46,XX and an unusually large Q-bright satellite on one chromosome 22. In situ hybridization with the 3,4-kb probe to the metaphase preparations of family members indicated that the additional Q-bright material in the proband's variant chromosome 18 derived from the Y chromosome of his father, and not from the variant chromosome 22 of his mother. On Southern hybridization, the proband had approximately twice the amount of 3,4-kb repeats per cell as his father. These observations suggest a de novo genetic rearrangement in the proband which probably occurred during the father's spermatogenesis.     

Coexistence of inverted Y, chromosome 15p+ and abnormal phenotype.

In this study, we report conventional and molecular cytogenetic studies in a patient with multiple anomalies who is a carrier of a pericentric inversion on chromosome Y and a chromosome 15p+. His parents were phenotypically normal. The father is a carrier of a pericentric inversion of chromosome Y, and the mother carries a large chromosome 15p+ variant. The inverted Y chromosome was demonstrated by GTG- and CBG-banding, and DAPI-staining. The presence of extra chromosomal material on the chromosome 15p, that was C-band and DAPI positive, was demonstrated by trypsin G-banding. This suggests that the extra chromosomal material contained repetitive DNA sequences. NOR-staining indicated the presence a nuclear organizer region at the junction of the chromosome 15p+ material. Fluorescence in situ hybridization (FISH), with chromosome X and Y painting probes, alpha- and classic-satellite probes specific for chromosome Y, alpha- and beta-satellite III probes for chromosome 15 were used to elucidate the nature of both the inverted Y chromosome and chromosome 15p+. The result with chromosome X and Y painting probes, alpha-satellite, classic-satellite, and DYS59 probes specific for chromosome Y revealed the rearrangement of the Y chromosome was an inv(Y)(p11.2q11.22 or q11.23). FISH with alpha-satellite and beta-satellite III probes for chromosome 15 demonstrated that the extra chromosomal material on the chromosome 15 probably represents beta-satellite III sequences. The possible roles of the simultaneous occurrence of an inverted Y and the amplified DNA sequence on chromosome 15p in the abnormal phenotype of the proband are discussed.     

A distinctive phenotype associated with an interstitial deletion 6q14 contained within a de novo pericentric inversion 6 (p11.2q15)

This report describes a nearly 25-year-old female with an interstitial deletion of band 14 in the long arm of one chromosome 6 (6q14). The deletion is contained within a de novo pericentric inversion with breakpoints in 6p11.2 and 6q15 (Karyotype 46,XX, del(6)(q13q15),inv(6)(p11.2q15). The distal breakpoint of the deletion and the pericentric inversion at 6q15 are the same, but the proximal breakpoints differ. Since cells with other chromosomal findings were not detected in cultured lymphocytes and fibroblasts, chromosome mosaicism seems unlikely. Thus, it is assumed that the inversion and the deletion originated from the same event. The development of a distinctive phenotype in the patient was observed over a period of 22 years. It includes characteristic dysmorphic facial features such as ocular hypertelorism, flat nasal bridge, prominent zygomatic bones, and a depressed glabella. A striking, non-progressive deficit of motor control is manifest in an inability to use her hands properly and a broad-based slow-motion-like gait. Although severely deficient in abstract mental abilities and speech development, she is well adapted to family life and to a school for retarded individuals. Normal height and head circumference, and reduced sensitivity to pain are noteworthy. Presumably the deletion caused the phenotype and the distinct behavioral pattern. This patient probably represents a novel chromosomal phenotype that results from aggregate haploinsufficiency of gene loci in the deleted region.     

一例t（Y;15）并t（14;21）复合易位的细胞与分子遗传学研究

本文对一便生育过先天愚型儿的个体刊进行了细胞与分子遗传学研究。发现先证者拥有ｔ（１４;２１）用一个短臂增大变异为１５号标记染色体。通过Ｇ－显带、Ｃ－显带、Ｑ－显带、硝酸银染色及Ｙ染色体长臂异染色质区特异控针ｐＹ３．４对先证者基因组ＤＮＡ的斑点杂交和中期染色体的原位杂交,证实变异部分由Ｙ染色体长臂异染色质区易位所形成,从而排除了巨大随体的存在或其他染色体参与重排形成变的可能性,结果表明,常规显带与染     

Inherited pericentric inversion of chromosome no. 2 with Robertsonian translocation (13q 14q) resulting in trisomy for chromosome 13q

This report includes a patient with an inherited pericentric inversion of chromosome No. 2 in addition to a Robertsonian translocation resulting in trisomy for chromosome 13q. The chromosomal constitution of the proband was 46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter); t(13,14) (13qter leads to 13p11 : : 14q11 leads to 14qter). Sequential QFQ, RFA and GTG banding techniques were employed on the chromosomes of all family members. The chromosomal constitutions of the father and his first child were normal while the mother had an inversion of chromosome No. 2 [46,XX,inv(2) (pter leads to p11 : : q14 leads to p11 : : q14 leads to qter)]. The proband inherited this abnormal chromosome. In addition, she had a de novo Robertsonian translocation involving chromosomes 13q and 14q resulting in trisomy of chromosome 13q.