Microdeletions in the y chromosome of infertile men

Testis-expressed gene 11 (TEX11) is an X-linked gene and essential for meiotic recombination and chromosomal synapsis. TEX11 deficiency causes meiotic arrest and male infertility, and many TEX11 mutations have been found in azoospermic and infertile men. This study reported one novel TEX11 mutation (2653G → T, in exon 29, GenBank accession number, NM_031276) in two brothers with azoospermia. This mutation was firstly screened out by whole-exome sequencing (WES) and further verified by amplifying and sequencing the specific exon 29. Surprisingly, the same exonic missense mutation (W856C) was observed in two brothers but not in their mother. Histological analysis of testicular biopsy from both brothers revealed meiotic arrest and no post-meiotic round spermatids and mature spermatozoa were observed in the seminiferous tubules. TEX11 expression was observed strongly in spermatogonia and weakly in spermatocytes, but not in Sertoli cells and interstitial cells. We identified one novel TEX11 mutation in two brothers and summarized the literature regarding TEX11 mutations and male infertility. This study and previous literature indicate that TEX11 mutations are closely associated with male infertility, especially azoospermia, although auxiliary clinical analyses are needed to figure out the causes of male infertility.

/pdf/a-novel-tex11-mutation-induces-azoospermia-a-case-report-of-sqskr21v3p.pdf

A novel TEX11 mutation induces azoospermia: a case report of infertile brothers and literature review

Ring chromosome abnormalities are rare abnormalities potentially involving any chromosome and the vast majority of previously reported cases were seen in patients with various congenital malformations and mental retardation. On the other hand, only few subjects carrying ring chromosomes and with normal phenotype have been described [1]. Until now only 30 cases of ring autosome 9 (r(9)) have been reported in the literature [2]. The prevalence of this pathology is 1 in 50,000 foetuses and in the majority of cases serious malformations were described [3].

The most typical ring formation occurs after terminal deletion and fusion of the p arm and the q arm and under this process genetic material can be lost [4]. The most common breakpoints are found between 9p24-p22 and 9q33-q34, but end-to-end fusion of palindromic telomere sequences have also been reported [5].

The Danish cytogenetic register, which contains data from all cytogenetic testing in Denmark from 1960 onwards (altogether 345,000 cases), has sparse information on two r(9) cases: a female, born in 1946, who died childless and a girl born 2008 for whom no more information is available.

The most frequent malformations reported in connection with r(9) are related to the deleted regions of both arms and include growth and psychomotor retardation, facial dysmorphism, microcephaly, cardiac malformations, limb and skeletal anomalies [5]. Microdeletions in the telomeric region of the long arm of chromosome 9 were found in patients with Kleefstra syndrome [6, 7], whereas microdeletions of the telomeric end of the short arm may lead to 46,XY gonadal dysgenesis [2].

The literature regarding genital malformations in males with the presence of r(9) is very sparse; however the following malformations have previously been reported: cryptorchidism, hypospadias and micropenis [7]. Until now it is not clear whether the presence of r(9) affects spermatogenesis, as most cases have been described in young boys. Moreover, the literature is sparse regarding phenotypic details and sperm status. However azoospermia has previously been reported in males with other ring chromosomes, affecting chromosomes 12, 15, 21 and 22 [4, 8, 9].

The distal part of 9p is quite polymorphic and larger deletions of this region are often sporadic, combined with head/facial malformations like trigonocephaly, long philtrum, hypertelorism and micrognatia [2]. However, different gonadal disorders like complete gonadal dysgenesis, ovotestis, cryptorchidism and/or hypoplastic testes have also been described and typically these disorders were caused by deletions of three DMRT genes (DMRT1, DMRT2 and DMRT3) on the 9p24 region, with DMRT1 being the prime candidate [10]. These genes are involved in downstream pathways of sex determination; however the exact molecular mechanism is unclear.

The present case describes an azoospermic male with r(9) and this case further highlight that autosomal ring chromosomes can be involved in male infertility.

Azoospermia and ring chromosome 9--a case report.

This study aimed to identify the cause of azoospermia in a 38-year-old infertile man who was referred for genetic testing. Cytogenetic evaluation was performed by G-banding, C-banding, and FISH using centromeric probes for chromosomes X and Y and showed the presence of a monocentric isochromosome Y with a complex, mosaic karyotype 45,X/46,X,i(Y)(q10)/46,XX/47,XX,i(Y)(q10). Multiplex PCR for the commonly deleted genes in the AZFa, AZFb, and AZFc regions of the Y chromosome was performed and indicated the presence of all 3 regions. Further, PCR amplification followed by DNA sequencing of the SRY gene was done, which ruled out mutations in that gene. To identify the position of the SRY gene, FISH using a locus-specific probe was used and showed that the gene had been translocated to chromosome 3. Subtelomere FISH for 3q and Yp evidenced that the subtelomeric region of the Y chromosome was found on the terminal region of 3q. The clinical symptoms of the patient can be attributed to this abnormal genotype. The importance of genetic testing in infertile patients and the need for genetic counselling to prevent the transmission of the defect are emphasized.

Localization of the SRY Gene on Chromosome 3 in a Patient with Azoospermia and a Complex Karyotype 45,X/46,X,i(Y)(q10)/46,XX/ 47,XX,i(Y)(q10).

A patient presenting with azoospermia was referred for genetic evaluation, and upon karyotyping, he was revealed to have two cell lines-mos46,X,ider(Y)(q10)inv(Y)(p11.3q11.1)/45,X. Further cytogenetic studies such as C banding and fluorescence in situ hybridization were performed, which revealed an inversion duplication of a segment of the Y chromosome; hence, the derivative chromosome contained two SRY genes but only one centromere. Y chromosome microdeletion studies were performed in select STS sequences of AZFa, AZFb and AZFc regions and found to be negative for microdeletions. For such a case of infertility, the couple was advised to undergo artificial reproductive techniques with the help of donor spermatozoa.

Rare case of monocentric isochromosome Y with inversion duplication of p arm in patient diagnosed with azoospermia.

Objective
To report the cytogenetic and molecular genetic analysis of the first two cases of non-chimerism and chimerism karyotype in Chinese male patients who suffer from azoospermia, which may be caused by pseudo dicentric Y chromosomes.

/pdf/non-chimerism-and-chimerism-pseudo-dicentric-y-chromosome-6hpiveq1wz.pdf

Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population

OBJECTIVE To investigate the clinical phenotype and genetic characteristics of an azoospermia patient with ring 22 chromosome syndrome. METHODS We analyzed the clinical data of an azoospermia patient with ring 22 chromosome syndrome and reviewed relevant literature. RESULTS The patient was a short 29-year-old male, with bilateral testes small in size and soft in texture. Seminal examination indicated azoospermia. Chromosome analysis showed the karyotype of the patient to be 46, XY, r (22) (p11, q25). The level of testosterone was low, and the testicular tissue was brittle and easy to break. Pathological microscopy revealed reduced number of Sertoli cells and germ cells in the seminiferous tubules and thinner layers of cells. All the germ cells were spermatogonia. Neither spermatocytes nor sperm cells were found, which suggested complete spermatogenic failure. Mild interstitial fibrosis was visible in part of the seminiferous tubule walls. CONCLUSION Patients with ring 22 chromosome syndrome usually represent normal clinical phenotypes. However, this kind of genetic abnormality often induces severe testicular damage and spermatogenic arrest, which may result in azoospermia.

[Ring 22 chromosome syndrome induced azoospermia: a case report and literature review].

21-hydroxylase deficiency (21-OHD) caused congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic disorders resulting from mutations in genes involved with cortisol (CO) synthesis in the adrenal glands. Testicular adrenal rest tumors (TARTs) are rarely the presenting symptoms of CAH. Here, we describe a case of simple virilizing CAH with TARTs, in a 15-year-old boy. The patient showed physical signs of precocious puberty. The levels of blood adrenocorticotropic hormone (ACTH), urinary 17-ketone steroids (17-KS), dehydroepiandrosterone sulfate (DHEA-S), and serum progesterone (PRGE) were elevated, whereas those of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and CO were reduced. Computed tomography (CT) of the adrenal glands and magnetic resonance imaging (MRI) of the testes showed a soft tissue density (more pronounced on the right side) and an irregularly swollen mass (more pronounced on the left side), respectively. Pathological examination of a specimen of the mass indicated polygonal/circular eosinophilic cytoplasm, cord-like arrangement of interstitial cells, and lipid pigment in the cytoplasm. Immunohistochemistry results precluded a diagnosis of Leydig cell tumors. DNA sequencing revealed a hackneyed homozygous mutation, I2g, on intron 2 of the CYP21A2 gene. The patient's symptoms improved after a three-month of dexamethasone therapy. Recent radiographic data showed reduced hyperplastic adrenal nodules and testicular tumors. A diagnosis of TART should be considered and prioritized in CAH patients with testicular tumors. Replacement therapy using a sufficient amount of dexamethasone in this case helps combat TART.

https://www.ijfs.ir/article_45351_2ae9cdfab26e2d6ab354a12ef1209b44.pdf

A Case of Bilateral Testicular Tumors Subsequently Diagnosed as Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Lu Ding

Author Tools

Chat about Author

Papers

Non-chimerism and chimerism pseudo dicentric Y chromosome: two case reports about azoospermia and cytogenetic/molecular genetic analysis in the Chinese population

[Ring 22 chromosome syndrome induced azoospermia: a case report and literature review].

A Case of Bilateral Testicular Tumors Subsequently Diagnosed as Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.