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

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.

Telomeric association between chromosomes Y and 19 in a mosaic Turner with primary ovarian insufficiency.

A rare case of telomeric association between Y and 19 chromosomes in a 24-year-old patient with primary ovarian insufficiency is being reported. Clinical evaluation revealed a webbed neck, high-arched palate and short stature with absence of axillary hair. Small uterus and streak gonads were noted on pelvic ultrasonography. Cytogenetic analysis showed a mosaic karyotype 46,X,tas(Y;19)(p11.3;q13.4)/45,X with two centromeres on the derivative chromosome. Fluorescence in situ hybridization (FISH) for X and Y centromere, SRY gene and subtelomeric FISH showed that signals for SRY and heterochromatin of Y chromosome were found at the base of chromosome 19 and the subtelomere regions of 19q and Yp were intact. Multiplex polymerase chain reaction was done to check for common microdeletions in AZF region and showed no microdeletion. Due to the presence of Y chromosome, laparoscopic examination followed by gonadal histopathology was done and confirmed the presence of ovotestes. Gonadectomy was performed to avoid future risk of gonadoblastoma. Artificial reproductive techniques using donor oocytes was suggested to the couple.

A rare case of de novo balanced reciprocal Y:1 chromosomal translocation in patient presenting with azoospermia.

Presence of chromosomal anomalies is well known to be associated with reproductive failures where the incidence of chromosomal translocations is higher. Y:1 chromosomal translocations are reported to be rare and may have variable phenotypic effects such as infertility amongst others. The patient presented with azoospermia and dyslipidemia and coronary arterial disease. Cytogenetic tests such as karyotyping revealed the translocation, and fluorescent in situ hybridisation was performed to investigate the presence or absence of SRY gene. The SRY gene was found to be located on the p arm of the derivative Y chromosome. The test for Y chromosome microdeletions was reported to be negative for the AZF gene regions tested. Here we report the first case of Y:1 chromosomal translocation involving the break points (q11.2;p21) from India.

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).

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.

The Importance of Cytogenetics and Associated Molecular Techniques in the Management of Patients Carrying Robertsonian Translocation and Their Pregnancy Outcome by Intracytoplasmic Sperm Injection.

OBJECTIVE: The present study outlines three cases of a Robertsonian translocation and the consequences for the initiation of pregnancy by intracytoplasmic sperm injection (ICSI). Three case histories are presented documenting structural chromosome abnormalities in infertile males. MATERIALS AND METHODS: Semen analysis was performed according to the World Health Organization guidelines. Chromosome analysis was performed using G-banding. Y chromosome microdeletions were detected by multiplex polymerase chain reaction assays. RESULTS: Cytogenetic analysis revealed Robertsonian translocation 45,XY,der(14;21)(q10;q10) in a male with severe oligoasthenoteratozoospermia (SOAT) after three subsequent ICSI treatments were unsuccessful. The second case involved a Robertsonian translocation 45,XY,der(13,14)(q10;q10) with SOAT detected in a male after one pregnancy loss. Third case involved a Robertsonian translocation 45,XY,der(13,14)(q10;q10) with SOAT. CONCLUSION: This case series emphasize the necessity of cytogenetic analysis of couples with primary infertility and recurrent miscarriages before any assisted reproductive technology is performed. For couples in whom one or more partners have a translocation, prenatal genetic diagnosis/preimplantation genetic diagnosis is recommended.

Complete Androgen Insensitivity Syndrome in Three Generations of Indian Pedigree.

BACKGROUND: Androgen insensitivity syndrome or testicular feminization syndrome is a rare X-linked recessive disorder, which encompasses a wide range of phenotypes that are caused by numerous different mutations in the androgen receptor gene. Complete androgen insensitivity syndrome occurs when the body cannot use androgens at all. People with this form of the condition have the external sex characteristics of females, but do not have a uterus and therefore do not menstruate and are unable to conceive a child (infertile). METHODS: In this paper, we report three cases of familial complete androgen insensitivity syndrome who presented with primary amenorrhea. RESULTS: Physical examination, ultrasonography studies, and biochemical, karyotype, and molecular cytogenetic analyses were conducted. Based on the findings, they were diagnosed and confirmed as having complete androgen insensitivity syndrome. CONCLUSION: A multidisciplinary team is needed from disclosure of the diagnosis, gender assignment, surgical management, hormonal replacement therapy, to counseling and support.

An investigation of Ph(1) chromosome in Chronic Myeloid Leukemia patients with different treatment modalities and hematological features.

Chronic myeloid leukemia (CML) is characterized by a Ph(1) chromosome that derives through a translocation between chromosomes 9 and 22, i.e., t (9;22). Identifying the Ph(1) chromosome through cytogenetic analysis is an important aspect of CML diagnosis. The aim of this study was to determine the significance of cytogenetic analysis in the diagnosis of CML as well as to find out a relationship between chromosomal abnormalities and CML patients in different stages of treatment. Six CML patients were investigated for this study. The presence of Ph(1) chromosome was detected at different times of treatment using GTG banding on peripheral blood or bone marrow aspirations, and the results were analyzed using cytovision workstation. Hematological features were compared between newly diagnosed patients and patients under treatment. The Ph(1) chromosome was strongly associated with all cases of CML. The regression of Ph(1) chromosomes differed for each patient depending on the treatments and individual response to specific treatments.

Ring chromosome 8 and trisomy 8 in a patient with acute myeloid leukemia.

We describe a child with Acute Myeloid Leukemia (AML M7) with trisomy 8 and ring chromosome 8. Ring chromosome 8 associated with AML is uncommon and is reported to have a poor outcome. The combination of trisomy 8 and ring chromosome 8 has not been previously reported. This 15-month-old girl had presented with a history of fever, weight loss of 1 kg, gum bleeds and pallor. Clinical examinations revealed no nodes or organomegaly. Investigations revealed pancytopenia and elevated serum LDH. Bone marrow aspirate confirmed the presence of myeloid blasts positive only for CD 41 and CD 61 on flow cytometry. Chromosomal analysis from the bone marrow showed 46, XX [13]/ 47, XX, +8[2]/ 47, XX, +r (8) [5]. The child was treated as per UK MRC AML protocol (ADE 10+3+5). Bone marrow on day 21 post-induction was in morphological remission. Repeat karyotyping revealed 46,XX suggesting that the patient was in cytogenetic remission. Cytogenetic sub grouping in AML patients provides guidelines for the choice of optimal treatment strategy. There was no HLA matched family donor and hence an unrelated donor search was commenced as she was in the group with unfavourable cytogenetics. She developed acute myelofibrosis soon after the second cycle of chemotherapy with swinging fever and rapidly enlarging spleen. The marrow showed 11% blasts with intense fibrosis. She went through a stormy period during conditioning for unrelated stem cell transplantation. She passed away on day 11 post transplantation of veno-occlusive disease of liver and multiorgan failure. This case illustrates the poor outcome in paediatric AML with trisomy and ring chromosome 8.