A simplified gene-specific screen for Y chromosome deletions in infertile men

Teng, Yen-Ni; Lin, Ying; Tsai, Yung Chieh; Hsu, Chao Chin; Kuo, Pao Lin; Lin, Yung Ming

doi:10.1016/j.fertnstert.2006.11.050

Cited by 9 publications

(6 citation statements)

References 48 publications

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“…From January 2005 to July 2007, infertile men with abnormal semen parameters were enrolled into the study. They underwent a comprehensive examination, including a detailed medical history, physical examination, hormone profiles and a molecular test for Y-chromosome micro-deletions, as described previously [76]. Patients with Y-chromosomal microdeletion have been excluded from the study.…”

Section: Methodsmentioning

confidence: 99%

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

et al. 2012

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It is estimated that 10–15% of couples are infertile and male factors account for about half of these cases. With the advent of intracytoplasmic sperm injection (ICSI), many infertile men have been able to father offspring. However, teratozoospermia still remains a big challenge to tackle. Septins belong to a family of cytoskeletal proteins with GTPase activity and are involved in various biological processes e.g. morphogenesis, compartmentalization, apoptosis and cytokinesis. SEPTIN12, identified by c-DNA microarray analysis of infertile men, is exclusively expressed in the post meiotic male germ cells. Septin12+/+/Septin12+/− chimeric mice have multiple reproductive defects including the presence of immature sperm in the semen, and sperm with bent neck (defect of the annulus) and nuclear DNA damage. These facts make SEPTIN12 a potential sterile gene in humans. In this study, we sequenced the entire coding region of SEPTIN12 in infertile men (n = 160) and fertile controls (n = 200) and identified ten variants. Among them is the c.474 G>A variant within exon 5 that encodes part of the GTP binding domain. The variant creates a novel splice donor site that causes skipping of a portion of exon 5, resulting in a truncated protein lacking the C-terminal half of SEPTIN12. Most individuals homozygous for the c.474 A allele had teratozoospermia (abnormal sperm <14%) and their sperm showed bent tail and de-condensed nucleus with significant DNA damage. Ex vivo experiment showed truncated SEPT12 inhibits filament formation in a dose-dependent manner. This study provides the first causal link between SEPTIN12 genetic variant and male infertility with distinctive sperm pathology. Our finding also suggests vital roles of SEPT12 in sperm nuclear integrity and tail development.

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Section: Methodsmentioning

confidence: 99%

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

et al. 2012

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“…Numerous studies have described partial AZFa deletions including the USP9Y or DDX3Y genes or in part of each (6)(7)(8)(9)(10)(11)(12)(13). The reported prevalence of partial AZFa deletions had a wide range (0.2%-11%), and the histologic picture ranged from normozoospermia to SCO.…”

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confidence: 99%

Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance?

Kleiman

Almog

Yogev

et al. 2012

Fertility and Sterility

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“…Among AZF genes, AZFc is the most commonly deleted interval in men with azoospermia or severe oligozoospermia [20],[39]. However in the outmost side, the blood leukocytes AZFc deletion frequency in azoospermia patients is reported to be 10–15%.…”

Section: Discussionmentioning

confidence: 99%

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

et al. 2017

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About 10–15% of non-obstructive azoospermia (NOA) patients show AZFc microdeletion in their blood leukocytes. However, if AZF genes were involved in impaired spermatogenesis, a higher frequency of chromosomal microdeletions was expected. In this study the frequency of AZFc microdeletion was compared with TTY2 gene family, i.e., TTY2A2A and TTY2A12A in blood leukocytes of NOA patients and normal fertile control. In the present study 30 normal fertile individuals with mean age of 35.0 ± 6.0 and 30 NOA patients with mean age of 34.0 ± 7.0 were screened for microdeletion of TTY2L2A and TTY2L12A at Yq11 and Yp11 respectively and sequence-tagged site (STS) markers for AZFc gene using multiplex PCR technique. At the first step karyotyping was done for all subjects using standard G-banding technique to identify patients with normal karyotype as well as non-affected normal controls for molecular analysis. Results showed no AZFc microdeletion in normal and NAO patients whereas one TTY2L2A microdeletion in normal control (3.3%) and 4 in NOA (13.3%) was observed ( p < 0.05). However our data indicated that 6 of 30 NOA patients (20%) showed TTY2L12A microdeletion whereas there was no observed microdeletion in normal control ( p < 0.01). Results indicate that the studied genes might be involved in impaired spermatogenesis more effective than the routinely screened AZF genes in infertile men. Therefore, screening these genes along with AZF genes might be valuable for infertile patients. The reason why these genes are deleted from Y chromosome is not known but might be associated with genomic instability induced by environmental physico-chemical genotoxic agents.

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A simplified gene-specific screen for Y chromosome deletions in infertile men

Cited by 9 publications

References 48 publications

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

SEPTIN12 Genetic Variants Confer Susceptibility to Teratozoospermia

Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance?

High frequency of microdeletion in TTY2 gene family in peripheral blood leukocytes of non-obstructive azoospermia patients

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