Individuals with 46,XX/XY chimerism can display a wide range of characteristics, varying from hermaphroditism to complete male or female, and can display sex chromosome chimerism in multiple tissues, including the gonads. The gonadal tissues of females contain both granulosa and germ cells. However, the specific sex chromosome composition of the granulosa and germ cells in 46,XX/XY chimeric female is currently unknown. Here, we reported a 30-year-old woman with secondary infertility who displayed a 46,XX/46,XY chimerism in the peripheral blood. FISH testing revealed varying degrees of XX/XY chimerism in multiple tissues of the female patient. Subsequently, the patient underwent preimplantation genetic testing (PGT) treatment, and 26 oocytes were retrieved. From the twenty-four biopsied mature oocytes, a total of 23 first polar bodies (PBs) and 10 second PBs were obtained. These PBs and two immature metaphase I (MI) oocytes only displayed X chromosome signals with no presence of the Y, suggesting that all oocytes in this chimeric female were of XX germ cell origin. On the other hand, granulosa cells obtained from individual follicles exhibited varied proportions of XX/XY cell types, and six follicles possessed 100% XX or XY granulosa cells. A total of 24 oocytes were successfully fertilized, and 12 developed into blastocysts, where 5 being XY and 5 were XX. Two blastocysts were transferred with one originating from an oocyte aspirated from a follicle containing 100% XY granulosa cells. This resulted in a twin pregnancy. Subsequent prenatal diagnosis confirmed normal male and female karyotypes. Ultimately, healthy boy-girl twins were delivered at full term. In summary, this 46,XX/XY chimerism with XX germ cells presented complete female, suggesting that germ cells may exert a significant influence on the sexual determination of an individual, which provide valuable insights into the intricate processes associated with sexual development and reproduction.

Turners\' syndrome, although common, is a complex syndrome that requires a multidisciplinary team to manage it. If undiagnosed prenatally or in childhood, Turners\' syndrome females often present later to gynaecologists with premature ovarian insufficiency or infertility as their primary presenting complaint. Timely diagnosis and management are key to improving health outcomes in women with Turners\' syndrome, as it is associated with multiple comorbidities which left untreated will result in excess morbidity and mortality. We hereby present a case of a 20-year-old female diagnosed to have Turner\'s syndrome with mosaicism of the X chromosome to highlight the wide array of clinical presentations it can have.
UNASSIGNED: case reports; infertility; sex chromosome aberrations; Turner syndrome.

Hemophilia is an inherited X-linked bleeding disorder characterized by deficiencies of factors VIII or IX. Concomitant X chromosome disorders can impact bleeding phenotype, complicating timely diagnosis and disease management. Herein, we describe three cases of female and male pediatric patients with hemophilia A or B diagnosed between 6 days and 4 years old in the setting of skewed X chromosome inactivation, Turner syndrome, or Klinefelter syndrome. All of these cases had significant bleeding symptoms, and two patients required initiation of factor replacement therapy. One female patient developed a factor VIII inhibitor similar to that described in males with hemophilia A.

Duchenne/Becker muscular dystrophy (DMD/BMD) is one of the most common progressive muscular dystrophy diseases with X-linked recessive inheritance. It is mainly caused by the deletion, duplication and point mutation of DMD gene. In rare cases, it is also caused by the destruction of DMD gene by chromosomal structural rearrangement. Here, we report a case of Duchenne/Becker Muscular dystrophy (DMD/BMD) with typical symptoms but unknown genetic defects after MLPA and next generation sequencing tests in other hospitals. Interestingly, we find a pericentric inversion of X chromosome (Chr.X: g. [31939463-31939465del; 31939466-131765063 inv; 131765064-131765067del]) in this patient. We then use the karyotyping, FISH, long-read sequencing and Sanger sequencing technologies to characterize the chromosome rearrangement. We find that this chromosomal aberration disrupt both the DMD gene and the HS6ST2 gene. The patient present with typical DMD symptoms such as muscle weakness, but no obvious symptoms of Paganini-Miozzo syndrome. Our results suggest that the destruction of DMD gene by structural rearrangement is also one of the important causes of DMD. Therefore, we suggest to provide further genetic testing for those DMD patients with unknown genetic defects through routine genetic testing. Cost-effective karyotyping and FISH should be considered firstly to identify chromosome rearrangements. Long-read sequencing followed by Sanger sequencing could be useful to locate the precise breakpoints. The genetic diagnosis of this case made it possible for reproductive intervention in the patient\'s family.
假肥大型肌营养不良(Duchenne/Becker muscular dystrophy，DMD/BMD)是一种最常见的进行性肌营养不良疾病，呈X-连锁隐性遗传，主要由DMD基因的缺失、重复及点突变所致，极少数病例是由于染色体结构重排破坏了DMD基因而引起疾病的发生。本文报告了1例经多重连接探针扩增技术(multiplex ligation-dependent probe amplification，MLPA)和下一代测序检测后原因未明的、具有典型症状的DMD患者。采用核型分析、FISH分析及三代测序、Sanger测序综合分析发现，患者存在母源性的X染色体臂间倒位(Chr.X:g. [31939463-31939465del; 31939466-131765063 inv; 131765064-131765067del])半合子变异。由于该变异破坏了DMD基因和HS6ST2基因，因此推测该变异是患者发病的遗传学病因。患者表现肌无力等典型的DMD症状，没有明显的Paganini-Miozzo综合征相关症状。本病例的明确诊断，提示结构重排破坏DMD基因也是导致DMD重要原因之一；常规遗传学检测阴性的患者应考虑核型分析、FISH验证等结构重排变异检测技术，通过三代测序技术能确定大概的重排断点位置，Sanger测序可明确断点区域序列。本病例报告通过明确的遗传学诊断为该患者所在家庭进行生殖干预、降低再生育风险提供了诊疗基础。.

North Caucasus has always been a residence of a lot of different authentic ethnic groups speaking different languages and still living their traditional lifestyle. The diversity appeared to be reflected in the accumulation of different mutations causing common inherited disorders. X-linked ichthyosis represents the second most common form of genodermatoses after ichthyosis vulgaris. Eight patients from three unrelated families of different ethnic origin, Kumyk, Turkish Meskhetians, and Ossetian, with X-linked ichthyosis from the North Caucasian Republic of North Ossetia-Alania were examined. NGS technology was implied for searching for disease-causing variants in one of the index patients. Known pathogenic hemizygous deletion in the short arm of chromosome X encompassing the STS gene was defined in the Kumyk family. A further analysis allowed us to establish that likely the same deletion was a cause of ichthyosis in a family belonging to the Turkish Meskhetians ethnic group. In the Ossetian family, a likely pathogenic nucleotide substitution in the STS gene was defined; it segregated with the disease in the family. We molecularly confirmed XLI in eight patients from three examined families. Though in two families, Kumyk and Turkish Meskhetian, we revealed similar hemizygous deletions in the short arm of chromosome X, but their common origin was not likely. Forensic STR markers of the alleles carrying the deletion were defined to be different. However, here, common alleles haplotype is hard to track for a high local recombination rate. We supposed the deletion could arise as a de novo event in a recombination hot spot in the described and in other populations with a recurrent character. Defined here are the different molecular genetic causes of X-linked ichthyosis in families of different ethnic origins sharing the same residence place in the Republic of North Ossetia-Alania which could point to the existing reproductive barriers even inside close neighborhoods.

Somatic cell nuclear transfer (SCNT) is an asexual reproductive technique where cloned offspring contain the same genetic material as the original donor. Although this technique preserves the sex of the original animal, the birth of sex-reversed offspring has been reported in some species. Here, we report for the first time the birth of a female foal generated by SCNT of a male nuclear donor. After a single SCNT procedure, 16 blastocysts were obtained and transferred to eight recipient mares, resulting in the birth of two clones: one male and one female. Both animals had identical genetic profiles, as observed in the analysis of 15-horse microsatellite marker panel, which confirmed they are indeed clones of the same animal. Cytogenetic analysis and fluorescent in situ hybridization using X and Y specific probes revealed a 63,X chromosome set in the female offspring, suggesting a spontaneous Y chromosome loss. The identity of the lost chromosome in the female was further confirmed through PCR by observing the presence of X-linked markers and absence of Y-linked markers. Moreover, cytogenetic and molecular profiles were analyzed in blood and skin samples to detect a possible mosaicism in the female, but results showed identical chromosomal constitutions. Although the cause of the spontaneous chromosome loss remains unknown, the possibility of equine sex reversal by SCNT holds great potential for the preservation of endangered species, development of novel breeding techniques, and sportive purposes.

BACKGROUND: Chromosome Xp21 deletion syndrome is a rare X-linked recessive defect that occurs as a result of multiple gene deletions, including Glycerol kinase (GK) and its neighboring genes, dystrophin, which causes Duchenne muscular dystrophy (DMD), and NR0B1, which causes congenital adrenal hypoplasia (CAHhttps://www.omim.org/entry/300200). Patients usually present with glycerol kinase deficiency, congenital adrenal hypoplasia, Duchenne muscular dystrophy, hyperglycerolemia, and glyceroluria, associated with DMD and/or CAH, growth failure, myopathy, osteoporosis, mental retardation, and psychomotor retardation.
METHODS: Herein, we report a 3-year- old boy from Iraq who had bloody diarrhea, food intolerance and abdominal cramp, adrenal insufficiency, recurrent fevers, tuberculosis (TB) infection, cervical abscess, oral thrush, cervical and mediastinal lymphadenopathies, developmental delay, and undescended testis. His parents are non-consanguine and had no family history of diseases. Next generation sequencing demonstrated a hemizygote deletion in chromosome X.
CONCLUSIONS: Loss of a large part of the X-chromosome most likely can explain the clinical findings of this patient. Contiguous gene deletion syndrome in Xp21 should be considered after diagnosing adrenal insufficiency to treat metabolic complications efficiently.

Chronic myeloid leukemia (CML) is characterized by the reciprocal translocation between chromosomes 9 and 22: t(9;22)(q34;q11). However, 5-10% of patients with CML have complex variant translocations involving at least a third chromosome; only a few cases affect the X chromosome. Therefore, the data available regarding their features and the response to treatment is limited. In the present report, a case of a variant Philadelphia translocation t(X;9;22)(q22?;q34;q11.2) identified in a 51-year-old female with a newly diagnosed CML is described. The patient was treated with nilotinib. A major molecular response was observed after 12 months of starting treatment. Deep molecular response was obtained 20 months later and maintained after the 110-month follow-up. Additionally, a literature review was performed, with the aim of comprehending the complex clinical and biological characteristics of CML cytogenetic variants involving the X chromosome.

BACKGROUND: Small copy number variations confined to the placenta are extremely rare findings in chorionic villus sampling, nonetheless of great clinical importance. To the best of our knowledge, this is the first reported case of confined placental mosaicism for an intragenic Duchenne muscular dystrophy (DMD) gene deletion.
METHODS: We describe a pregnant woman where confined placental mosaicism for an intragenic DMD deletion was detected. She was referred for a chorionic villus sampling due to an increased risk of trisomy 21 derived from combined first trimester screening. Rapid aneuploidy detection showed a male fetus with normal results for chromosomes 13, 18 and 21. A chromosomal microarray demonstrated a deletion of exons 61-62 in the DMD gene in approximately 50% of the cells. A follow-up analysis on amniotic cells showed a normal result for the DMD gene. Hence, confined placental mosaicism was confirmed.
CONCLUSIONS: We propose tissue specific fragile sites as a possible theoretical mechanism for the formation of submicroscopic copy number variations and highlight that the finding of DMD deletion mosaicism in a chorionic villus sample might be isolated to the placenta. Therefore, confirmation by amniocentesis is of crucial clinical importance to avoid misdiagnosis of the fetus.

Klinefelter syndrome is a rare chromosomal disorder with at least one extra X chromosome in males resulting in male hypogonadism, androgen deficiency and impaired spermatogenesis. It is associated with an increased risk of certain malignancies; including leukemia, breast cancer, non-Hodgkin\'s lymphoma and mediastinal germ cell tumors, however, testicular tumors are rare in men with Klinefelter syndrome. Testicular epidermoid cysts are rare benign tumors affecting the testes. We report a case of bilateral testicular epidermoid cysts in a 30-year-old man known to have Klinefelter syndrome. He had an incidental finding of bilateral hard irregular-surfaced testes during routine assessment for testosterone replacement therapy. Biochemical investigation confirmed primary hypogonadism and ultrasound imaging demonstrated bilateral solid testicular masses with no blood flow seen within the lesions. The patient went on to have a right-sided radical orchiectomy with left-side sparing. The histology revealed features in keeping with that of a testicular epidermoid cyst with no evidence of malignancy. The patient was commenced on testosterone replacement therapy. This case emphasizes the importance of routine physical examination of the male external and internal genitalia when considering testosterone replacement therapy.