Ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions in a 17-year-old man

Papadimas, J.; Goulis, Dimitrios G.; Giannouli, Chariklia; Papanicolaou, A. N.; Tarlatzis, Basil C.; Bontis, J.

doi:10.1016/s0015-0282(01)02877-1

Cited by 35 publications

(20 citation statements)

References 4 publications

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“…The percentages of disomic sperm were not reported. These findings are in agreement with the observation of 45,X/46,XY chromosomal mosaicism in peripheral blood lymphocytes of men with AZF deletions (Siffroi et al, 2000;Jaruzelska et al, 2001;Papadimas et al, 2001) and the occurrence of AZFc deletions in men with Turner stigmata and 45,X/46,XY karyotype (Patsalis et al, 2002). However, FISH studies on sperm of men with AZF deletions are limited to the three men reported by Siffroi and colleagues (2000).…”

Section: Y Chromosome Long Arm Microdeletionssupporting

confidence: 91%

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities

Ferlin¹,

Garolla²

2005

Cytogenet Genome Res

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The most common type of karyotype abnormality detected in infertile subjects is represented by Klinefelter’s syndrome, and the most frequent non-chromosomal alteration is represented by Y chromosome long arm microdeletions. Here we report our experience and a review of the literature on sperm sex chromosome aneuploidies in these two conditions. Non mosaic 47,XXY Klinefelter patients (12 subjects) show a significantly lower percentage of normal Y-bearing sperm and slightly higher percentage of normal X-bearing sperm. Consistent with the hypothesis that 47,XXY germ cells may undergo and complete meiosis, aneuploidy rate for XX- and XY-disomies is also increased with respect to controls, whereas the percentage of YY-disomies is normal. Aneuploidy rates in men with mosaic 47,XXY/46,XY (11 subjects) are lower than those observed in men with non-mosaic Klinefelter’s syndrome, and only the frequency of XY-disomic sperm is significantly higher with respect to controls. Although the great majority of children born by intracytoplasmic sperm injection from Klinefelter subjects are chromosomally normal, the risk of producing offspring with chromosome aneuploidies is significant. Men with Y chromosome microdeletions (14 subjects) showed a reduction of normal Y-bearing sperm, and an increase in nullisomic and XY-disomic sperm, suggesting an instability of the deleted Y chromosome causing its loss in germ cells, and meiotic alterations leading to XY non-disjunction. Intracytoplasmic injection of sperm from Y-deleted men will therefore transmit the deletion to male children, and therefore the spermatogenic impairment, but raises also concerns of generating 45,X and 47,XXY embryos.

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Section: Y Chromosome Long Arm Microdeletionssupporting

confidence: 91%

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities

Ferlin¹,

Garolla²

2005

Cytogenet Genome Res

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“…Therefore, the presence of a Ynf chromosome is sometimes associated with additional pathologies: undescended testis and ambiguous genitalia (Thangaraj et al, 2003) indicating the 45,X0 cells also in the patients' gonad tissues. Similar pathologies were also described from patients with an AZFc deletion and a 45,X0 cell line (Siffroi et al, 2000;Jaruzelska et al, 2001;Papadimas et al, 2001). It suggests that Ynf chromosomes might be one of the final rearrangements of a generally unstable Y chromosome after the occurrence of a classical (i.e., complete) AZFc deletion (Vogt, 2004).…”

Section: Mapping Of Azf Deletions In Yq11supporting

confidence: 62%

AZF deletions and Y chromosomal haplogroups: history and update based on sequence

Vogt

2005

Human Reproduction Update

121

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AZF deletions are genomic deletions in the euchromatic part of the long arm of the human Y chromosome (Yq11) associated with azoospermia or severe oligozoospermia. Consequently, it can be assumed that these deletions remove Y chromosomal genes required for spermatogenesis. However, these 'classical' or 'complete' AZF deletions, AZFa, AZFb and AZFc, represent only a subset of rearrangements in Yq11. With the benefit of the Y chromosome sequence, more rearrangements (deletions, duplications, inversions) inside and outside the classical AZF deletion intervals have been elucidated and intra-chromosomal non-allelic homologous recombinations (NAHRs) of repetitive sequence blocks have been identified as their major cause. These include duplications in AZFa, AZFb and AZFc and the partial AZFb and AZFc deletions of which some were summarized under the pseudonym 'gr/gr' deletions. At least some of these rearrangements are associated with distinct Y chromosomal haplogroups and are present with similar frequencies in fertile and infertile men. This suggests a functional redundancy of the AZFb/AZFc multi-copy genes. Alternatively, the functional contribution(s) of these genes to human spermatogenesis might be different in men of different Y haplogroups. That raises the question whether, the frequency of Y haplogroups with different AZF gene contents in distinct human populations leads to a male fertility status that varies between populations or whether, the presence of the multiple Y haplogroups implies a balancing selection via genomic deletion/amplification mechanisms.

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“…(2)". Indeed, a man with ambiguous genitalia, 45,X/46,XY mosaic karyotype and AZFc deletion has been already reported [106]. Now screening the Y chromosome of 12 patients, who had a 45X/46XY karyotype and presented with Turner stigmata and sexual ambiguities a high incidence of AZFc deletions was found in this patient group as well [107].…”

Section: Icsi Transmission Of Azfc Deletions Can Cause Severe Gonadalmentioning

confidence: 67%

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Vogt¹

2004

CPD

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Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popular to unravel these netweorks with mouse gene knock-out mutants displaying reproductive defects. However, substantial arguments can be given for more functional studies directly on the human genes, because multiple reproductive proteins evolve quickly most likely for adopting to the specific needs of the species class. Prominent examples are mutations of the FSHR gene causing different pathologies in mouse and human and the DAZ gene family not found in the mouse genome but in the human genome with an essential male fertility function. Therefore this review is focussed on a comprehensive overview of human genes known with mutations causing male infertility (AR; AZF gene families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8-GREAT, LHR, POLG). Then some human genes are described well recognised as functional in spermatogenesis and male fertility although gene specific mutations causing infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2). They are designated as "spermatogenesis phase marker" or "male fertility index" genes, because they are useful tools for diagnosing the patient´s´ spermatogenesis disruption phase and for predicting the presence and quality of his mature sperms. Current therapeutic protocols for human male infertility do usually not cure the specific gene defect but try to bypass it using Artificial Reproductive Technology (ART). Putative imprinting defects in the early embryo probably associated with the used ART protocol and an increase of chromosome abnormalities in the ART offspring now strongly asks for a significant improvement of this outcome requesting urgently more basic research on the genes functioning in the human male germ line and during early human embryogenesis.

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Ambiguous genitalia, 45,X/46,XY mosaic karyotype, and Y chromosome microdeletions in a 17-year-old man

Cited by 35 publications

References 4 publications

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities

AZF deletions and Y chromosomal haplogroups: history and update based on sequence

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

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