Abnormal Y chromosome detection in infertile males using multiplex ligation‐dependent probe amplification

Dai, Xiaoying; Shi, Fang; Cheung, Clement S.K.; Li, Jue; Lin, Sheng Mou

doi:10.1111/and.14316

Cited by 3 publications

(1 citation statement)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phenotype has been associated with normal intelligence; however, semen examination has indicated oligospermia, asthenospermia and azoospermia. The oligospermia could be attributed to abnormal conjunctions during meiosis and the resulting inability to form gametes ( 16 ). Sex reversal syndrome accounted for 6.7% of abnormal karyotypes.…”

Section: Discussionmentioning

confidence: 99%

Molecular genetic analysis of 1,980 cases of male infertility

Chen

Guo

et al. 2023

Exp Ther Med

View full text Add to dashboard Cite

The present study aimed to investigate the occurrence of chromosomal karyotype abnormalities and azoospermia factor ( AZF ) microdeletion on the long arm of the Y chromosome (Yq) in infertile men, and to determine their association with infertility to ultimately improve clinical outcomes in these patients. A total of 1,980 azoospermic and oligospermic men from the outpatient department of the Fujian Maternity and Child Health Hospital (Fuzhou, China) were recruited between January 2016 and December 2019. Peripheral blood was used for karyotype analysis; AZF microdeletion analysis of the Yq was performed using capillary electrophoresis. Among the 1,980 patients, 178 had chromosomal abnormalities (9.0%; 178/1,980), of whom 98 had an abnormal number of chromosomes. Among the abnormal karyotypes, the most common was 47, XXY (80/178; 44.9%). AZF microdeletion on the Yq occurred at a rate of 10.66% (211/1,980); the most common type was the AZFb/c deletion (sY1192; 140/211; 66.4%). The present findings showed that karyotype abnormalities and AZF gene microdeletion are important drivers of male infertility. Specifically, men with Yqh- and del(Y)(q11) had a higher risk of AZF microdeletion. These results suggested that patient treatment could be personalized based on routine molecular genetic analysis, which could further alleviate the economic and emotional burden of undergoing redundant or ineffective treatments.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular genetic analysis of 1,980 cases of male infertility

Chen

Guo

et al. 2023

Exp Ther Med

View full text Add to dashboard Cite

show abstract

Systematic molecular analyses for 115 karyotypically normal men with isolated non-obstructive azoospermia

Muranishi,

Kobori,

Katoh-Fukui

et al. 2024

Human Reproduction

View full text Add to dashboard Cite

STUDY QUESTION Do copy-number variations (CNVs) in the azoospermia factor (AZF) regions and monogenic mutations play a major role in the development of isolated (non-syndromic) non-obstructive azoospermia (NOA) in Japanese men with a normal 46, XY karyotype? SUMMARY ANSWER Deleterious CNVs in the AZF regions and damaging sequence variants in eight genes likely constitute at least 8% and approximately 8% of the genetic causes, respectively, while variants in other genes play only a minor role. WHAT IS KNOWN ALREADY Sex chromosomal abnormalities, AZF-linked microdeletions, and monogenic mutations have been implicated in isolated NOA. More than 160 genes have been reported as causative/susceptibility/candidate genes for NOA. STUDY DESIGN, SIZE, DURATION Systematic molecular analyses were conducted for 115 patients with isolated NOA and a normal 46, XY karyotype, who visited our hospital between 2017 and 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS We studied 115 unrelated Japanese patients. AZF-linked CNVs were examined using sequence-tagged PCR and multiplex ligation-dependent probe amplification, and nucleotide variants were screened using whole exome sequencing (WES). An optimized sequence kernel association test (SKAT-O), a gene-based association study using WES data, was performed to identify novel disease-associated genes in the genome. The results were compared to those of previous studies and our in-house control data. MAIN RESULTS AND THE ROLE OF CHANCE Thirteen types of AZF-linked CNVs, including the hitherto unreported gr/gr triplication and partial AZFb deletion, were identified in 63 (54.8%) cases. When the gr/gr deletion, a common polymorphism in Japan, was excluded from data analyses, the total frequency of CNVs was 23/75 (30.7%). This frequency is higher than that of the reference data in Japan and China (11.1% and 14.7%, respectively). Known NOA-causative AZF-linked CNVs were found in nine (7.8%) cases. Rare damaging variants in known causative genes (DMRT1, PLK4, SYCP2, TEX11, and USP26) and hemizygous/multiple-heterozygous damaging variants in known spermatogenesis-associated genes (TAF7L, DNAH2, and DNAH17) were identified in nine cases (7.8% in total). Some patients carried rare damaging variants in multiple genes. SKAT-O detected no genes whose rare damaging variants were significantly accumulated in the patient group. LIMITATIONS, REASONS FOR CAUTION The number of participants was relatively small, and the clinical information of each patient was fragmentary. Moreover, the pathogenicity of identified variants was assessed only by in silico analyses. WIDER IMPLICATIONS OF THE FINDINGS This study showed that various AZF-linked CNVs are present in more than half of Japanese NOA patients. These results broadened the structural variations of AZF-linked CNVs, which should be considered for the molecular diagnosis of spermatogenic failure. Furthermore, the results of this study highlight the etiological heterogeneity and possible oligogenicity of isolated NOA. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Grants from the Japan Society for the Promotion of Science (21K19283 and 21H0246), the Japan Agency for Medical Research and Development (22ek0109464h0003), the National Center for Child Health and Development, the Canon Foundation, the Japan Endocrine Society, and the Takeda Science Foundation. The results of this study were based on samples and patient data obtained from the International Center for Reproductive Medicine, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER N/A.

show abstract

An integrated approach for improving clinical management of non‐obstructive azoospermia

Shi,

Liu,

Chen

et al. 2024

Andrology

View full text Add to dashboard Cite

BackgroundNon‐obstructive azoospermia is the most severe form of male infertility. A testicular biopsy is required for the diagnosis of non‐obstructive azoospermia, and the causal factors for non‐obstructive azoospermia remain unknown.ObjectivesTo reduce the risk of multiple biopsies and identify factors that contribute to non‐obstructive azoospermia, we proposed an integrated approach for the preoperative diagnosis and clinical management of non‐obstructive azoospermia by applying the chromosome‐spreading technique and whole‐exome sequencing.Materials and MethodsBetween July 2020 and December 2022, after ruling out definitive obstructive azoospermia and non‐obstructive azoospermia patients with testicular volume < 6 mL, 20 patients with non‐obstructive azoospermia who underwent preoperative testicular diagnostic biopsy using testicular sperm aspiration were subjected to retrospective analysis.ResultsMicroscopic examination identified four patients with sperm cells, and 16 without sperm cells. Routine pathological analysis classified one patient as normal spermatogenesis, three as hypospermatogenesis, five as maturation arrest, nine as Sertoli cell‐only, and two as unable to judge. With chromosome‐spreading technology using routine cell suspension samples for microscopic examination, 18 patient diagnoses were validated, and two patients without a definitive diagnosis were supplemented. Detection of the Y chromosome and a well‐organized whole‐exome sequencing analysis revealed potential genetic factors.Discussion and ConclusionThe full use of testicular biopsy is beneficial for the diagnosis of azoospermia, as it avoids the risk of multiple biopsies. Moreover, in combination with whole‐exome sequencing, clinicians can obtain more information regarding the pathogenesis of non‐obstructive azoospermia, which may guide treatment.

show abstract

Abnormal Y chromosome detection in infertile males using multiplex ligation‐dependent probe amplification

Cited by 3 publications

References 26 publications

Molecular genetic analysis of 1,980 cases of male infertility

Molecular genetic analysis of 1,980 cases of male infertility

Systematic molecular analyses for 115 karyotypically normal men with isolated non-obstructive azoospermia

An integrated approach for improving clinical management of non‐obstructive azoospermia

Contact Info

Product

Resources

About