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Partial chromosome Y deletion
Male sterility due to chromosome Y deletion is characterized by a severe deficiency of spermatogenesis. Chromosome Y deletions are a frequent genetic cause of male infertility.
ORPHA:1646Classification level: Disorder
Estimated prevalence is 1/2500.
Five to 10% of cases of azoospermia (absent sperm) or severe secretory-type oligospermia (<1 million spermatozoa/mL semen) are associated with microdeletions in the euchromatic portion of the Y-chromosome long arm, at the AZF locus (Azoospermia Factor). Several subregions are distinguished in the AZF locus. In this region, the structure of the Y-chromosome is rich in repeated palindromes and recombination between two flanking sequences sharing a high degree of homology leads to various deletions: 1) AZFa deletions (recombination between the sequences HERV15yq1 and HERV15yq2); the rarest - ii) AZFb or P5/proximal-P1 deletions, iii) AZFb+c deletions, of which two types are distinguished: P5/distal-P1 or P4/distal-P1 and iv) AZFc deletions caused by recombination between palindromes b2 and b4.
Diagnosis is made on the basis of azoospermia or oligozoospermia in otherwise healthy males after exclusion of other causes of infertility. Molecular diagnosis is made by PCR amplification of STS type sequences (sequence-tagged sites) from the AZFa, b, and c regions. AZFc deletions are the most frequent; they are associated with azoospermia or oligospermia, usually severe. Complete deletions of AZFa, AZFb+c and AZFb regions are always associated with azoospermia: testicular histology shows either total lack of germline cells (SCOS or Sertoli cell only syndrome) or more or less systematised arrested maturation of cells from the spermatogenetic cell lineage.
The mode of transmission follows a Y-linked pattern, with incomplete penetrance, but as deletions are often associated with infertility, they generally occur de novo. .
Management and treatment
All chromosome Y deletions do not necessarily lead to infertility: firstly, some deletions (especially some partial deletions) do not result in spermatogenesis defects; secondly, among men with severe oligospermia, some can father children without infertility treatment. Finally, when mature spermatozoa are found in the sperm or in the testicles, the infertility problem can be solved with medically assisted procreation techniques such as TESE (testicular sperm extraction)-ICSI (intracytoplasmic sperm injection). However, there is a risk of transmitting the microdeletion to every male infant.
- Clinical genetics review
- English (2019)