High incidence of Y-chromosome microdeletions in gonadal tissues from patients with 45,X/46,XY gonadal dysgenesis

Álvarez-Nava, Francisco; Puerta, Herminia; Soto, Marisol; Pineda, Lennie; Temponi, Ángel

doi:10.1016/j.fertnstert.2007.02.058

Cited by 19 publications

(15 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, our study gives credit to the theory, based on chromosome instability, of a link between a Y chromosome rearrangement that may predispose to anaphase lag and emergence of a 45,X cell line, and the occurrence of a disorder of sexual development, which has been proposed by other authors (5,12,14,15,16,17). Indeed, 63% of our patients had abnormal Y chromosome structure, which is higher than that found in 45,X/46,XY patients considering all phenotypes (20%) (10).…”

Section: Patient Gh Therapysupporting

confidence: 76%

See 1 more Smart Citation

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Martinerie

Morel²,

Pienkowski³

et al. 2012

European Journal of Endocrinology

View full text Add to dashboard Cite

Context: Gender assignment followed by surgery and hormonal therapy is a difficult decision in the management of 45,X/46,XY patients with abnormal external genitalia at birth considering the paucity of studies evaluating pubertal development and fertility outcome, most notably for patients raised as boys. Objective: The purpose of this study was to describe the pubertal course of 20 45,X/46,XY patients born with ambiguous genitalia and raised as boys. Methods: This is a multicenter retrospective study. Results: Mean age at study was 25.6G2.4 years. Eighty-five percent of the patients presented a 'classical' mixed gonadal dysgenetic phenotype at birth. Puberty was initially spontaneous in all but three boys, although in six other patients, testosterone therapy was subsequently necessary for completion of puberty. Sixty-seven percent of the remaining patients presented signs of declined testicular function at the end of puberty (increased levels of FSH and low levels of testosterone and/or inhibin B). Moreover, an abnormal structure of the Y chromosome, known to alter fertility, was found in 10 out of 16 (63%) patients. Two patients developed testicular cancer. Half of the patients have adult penile length of !80 mm. Mean adult height is 156.9G2 cm, regardless of GH treatment. Conclusions: In summary, 45,X/46,XY children born with ambiguous genitalia and raised as boys have an altered pubertal course and impaired fertility associated with adult short stature, which should, therefore, be taken into consideration for the management of these patients.

show abstract

Section: Patient Gh Therapysupporting

confidence: 76%

“…It is also encountered in 1% of male patients being consulted for infertility in the general population (13). Interestingly, a possible link between Y chromosome rearrangement and disorder of sexual development has been observed (5,12,14,15,16,17). Thus, the frequency of Y structural rearrangements was also evaluated in our patients.…”

Section: Introductionmentioning

confidence: 89%

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Martinerie

Morel²,

Pienkowski³

et al. 2012

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…All these abnormalities involved the sex chromosome, with a majority of mosaicism with isodicentric Y chromosome, 45,XO/ marker chromosome, or Yq deletion. An association between Y chromosome microdeletions and 45,X0/46,XY chromosomal mosaicism or isodicentric Y chromosome has been previously proposed [39][40][41][42]. Moreover, it was suggested that microdeletions in the Y chromosome might be associated with Y chromosomal instability leading to mitotic loss of the Y chromosome.…”

Section: Discussionmentioning

confidence: 98%

Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men

Kim

Choi

Park

et al. 2012

J Assist Reprod Genet

View full text Add to dashboard Cite

Objectives To determine the prevalence of Y chromosome microdeletions in infertile Korean men with abnormal sperm counts and to assess the clinical features and frequency of chromosomal abnormalities in Korean patients with microdeletions. Methods A total of 1,306 infertile men were screened for Y chromosome microdeletions, and 101 of them had microdeletions. These 101 men were then retrospectively studied for cytogenetic evaluation, testicular biopsy and outcomes of IVF and ICSI. ResultsThe overall prevalence of Y chromosome microdeletions in infertile men was 7.7 % (101/1,306). Most microdeletions were in the AZFc region (87.1%), including deletions of AZFbc (24.7 %) and AZFabc (8.9 %). All patients with AZFa, AZFbc and AZFabc deletions had azoospermia, whereas patients with an AZFc deletion usually had low levels of sperm in the ejaculate or in the testis tissues. Chromosomal studies were performed in 99 men with microdeletions, 36 (36.4%) of whom had chromosomal abnormalities. Among the infertile men with Y chromosome microdeletions in this study, the incidence of chromosomal abnormality was 48.6% in the azoospermic group and 3.7% in the oligozoospermic group. Among the 69 patients with microdeletions and available histological results, 100.0% of the azoospermic group and 85.7% of the oligozoospermic group had histological abnormalities. The frequency of both chromosomal abnormalities and histological abnormalities was higher in the azoospermic group compared to the oligozoospermic group. Thirtyfour ICSI cycles with either testicular (n014) or ejaculated spermatozoa (n020) were performed in 23 couples with men with AZFc microdeletion. Thirteen clinical pregnancies (39.4%) were obtained, leading to the birth of 13 babies. Conclusions The study results revealed a close relationship between microdeletions and spermatogenesis, although IVF outcome was not significantly affected by the presence of the AZFc microdeletion. Nevertheless, Y chromosome microdeletions have the potential risk of being transmitted from infertile fathers to their offspring by ICSI. Therefore, before using ICSI in infertile patients with severe spermatogenic defects, careful evaluations of chromosomal abnormalities and Y chromosome microdeletions screening should be performed and genetic counseling should be provided before IVF-ET.Capsule A close relationship exists between microdeletions and spermatogenesis, although IVF outcome was not significantly affected by the presence of an AZFc microdeletion.

show abstract

“…An association has been suggested between � chromosome microdeletions and severity of the phenotype in 45,X/46,X� (Álvarez-Nava et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

FISH, PCR and cytogenetic characterization in a girl with ambiguous genitalia and karyotype mos46,X,iso(Y)(qter→p11.3::p11.3→qter)[80]/45,X[17]/46,X,+mar[3]

Pereira

Pereira²,

Souza³

et al. 2008

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT.A cytogenetic study was carried out in a girl with virilized external genitalia, who showed a �aryotype containing a � isochro-, who showed a �aryotype containing a � isochroshowed a �aryotype containing a � isochroa �aryotype containing a � isochromosome in mosaic form: mos46,X,iso(�)(qter→p11.3::p11.3→qter) [80]/45,X[17]/46,X,+mar [3]. �he chromosome aberrations were con�he chromosome aberrations were confirmed by fluorescence in situ hybridization analysis, with both whole chromosome paint � probe and centromeric X chromosome probe. �he molecular analyses by PCR detected the presence of the SR�, DAZ and AMGY genes, confirming the presence of the whole long arm and almost whole short arm of the � chromosome. We suggest that the structural alteration of the � chromosome was a new mutation, which occurred in the initial mitotic divisions of the embryo, originally 46,X�. �he brea�points occurred on the distal extremity of the short arm with later fusion of its extremities producing a � isochromosome. �he later numerical alteration occurred as a consequence of chromosomal instability. Although almost all cells (80%) in peripheral blood belonged to the iso(�) line with a duplicated SR� gene, this did not determine male sexual differentiation in the patient. �he result of accurate evaluation provides correct sex assignment and the prevention of the neoplastic degeneration of a dysgenetic gonad.

show abstract

High incidence of Y-chromosome microdeletions in gonadal tissues from patients with 45,X/46,XY gonadal dysgenesis

Cited by 19 publications

References 8 publications

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Impaired puberty, fertility, and final stature in 45,X/46,XY mixed gonadal dysgenetic patients raised as boys

Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men

FISH, PCR and cytogenetic characterization in a girl with ambiguous genitalia and karyotype mos46,X,iso(Y)(qter→p11.3::p11.3→qter)[80]/45,X[17]/46,X,+mar[3]

Contact Info

Product

Resources

About