OBJECTIVE: To re-analyze a likely pathogenic variant in the Xq28 region identified by copy number variation sequencing (CNV-seq) through whole genome sequencing (WGS). METHODS: A fetus found to harbor a duplication in the Xq28 region by CNV-seq at Shengjing Hospital Affiliated to China Medical University in May 2023 was selected as the study subject. WGS was carried out for the fetus and its parents. Bioinformatic software was used to analyze the chromosomal structure and CNVs. Quantitative PCR (qPCR) was applied to determine the expression level of the MECP2 gene. This study has been approved by the Ethics Committee of Shengjing Hospital (Ethic No. 2013PS33K). RESULTS: A duplication (ChrX:153302641_153503563) and four breakpoints were identified on the X chromosome of the fetus' father. Bioinformatic analysis revealed that the duplicated region has involved exons 1 to 3 and part of the 5'-UTR of the MECP2 gene, which was inserted into the Xp11 region. Additionally, an inversion was detected in the Xp11 region adjacent to the duplicated segment. RT-PCR results showed normal level of MECP2 mRNA expression. The Xq28 duplication has not encompassed the entire MECP2 gene, nor disrupted its structure or altered its expression. CONCLUSION WGS has enabled more precise diagnosis of chromosomal structural variants and provided guidance for accurate genetic counseling for the affected families.
Humans ; Female ; Chromosomes, Human, X/genetics* ; DNA Copy Number Variations/genetics* ; Whole Genome Sequencing/methods* ; Methyl-CpG-Binding Protein 2/genetics* ; Pregnancy ; Male ; Adult

OBJECTIVE: To investigate the X-chromosome inactivation (XCI) patterns and origin in four children with Rett syndrome (RTT), and to explore the genetic basis of their phenotypic variability. METHODS: Four pediatric RTT cases diagnosed at Northwest Women's and Children's Hospital between August 1, 2022 and October 31, 2024 were enrolled. Clinical data were collected, and whole exome sequencing (WES) and Sanger sequencing were performed on the children and their parents to identify pathogenic variants. XCI analysis and linkage studies were conducted to determine the origin of variants and assess skewed XCI. This study was approved by the Medical Ethics Committee of the Northwest Women's and Children's Hospital (Ethics No. 21-036). RESULTS: WES and Sanger sequencing revealed that the four children carried the following MECP2 (NM_001110792.2) variants. c.916C>T (p.Arg306Cys), c.842delG (p.G281Afs*20), c.763C>T (p.R255X), and c.686C>T (p.Pro229Leu). The c.916C>T variant was maternally inherited, while the other three were de novo. All four variants have been previously reported: c.916C>T, c.842delG, and c.763C>T were classified as pathogenic, whereas c.686C>T was deemed likely pathogenic. XCI analysis demonstrated skewed inactivation in child 2 and 3 and their mothers, with maternal X-chromosome recombination during gametogenesis observed in child 3. All variants were located on the maternal X chromosome. CONCLUSION Skewed XCI is a common pathogenic mechanism in MECP2-related RTT, and MECP2 variants may exhibit a maternal origin bias. Clinical evaluation should incorporate XCI status for comprehensive genetic analysis.
Child ; Humans ; Chromosomes, Human, X/genetics* ; Exome Sequencing ; Methyl-CpG-Binding Protein 2/genetics* ; Mutation ; Rett Syndrome/genetics* ; X Chromosome Inactivation/genetics*

OBJECTIVE: To explore the mechanism for the occurrence and phenotypic characteristics of Turner syndrome based on a prenatally diagnosed case of a mosaic karyotype containing double pseudo-isodicentric X chromosome and a review of relevant literature. METHODS: A fetus diagnosed with increased risk for trisomy 21 at the Provincial Hospital Affiliated to Shandong First Medical University in August 2023 was selected as the study subject. Clinical data of the fetus was collected. Following amniocentesis, chromosomal G-banding karyotype analysis and chromosomal microarray analysis (CMA) were carried out. This study has been approved by the Ethics Committee of the Hospital (Ethics No.: SWYX No. 2022-287). RESULTS: The early-trimester screening suggested a high risk of trisomy 21 (1/19), with free β-hCG of 116 ng/mL (MoM value 2.35), PAPP-A of 0.394 ng/mL (MoM value 0.12), and NT value of 1.3 mm, though no abnormality was found in the fetus at 19 weeks gestation. The karyotype of amniocyte was determined as 46,X,psu idic(X)(p11.21)[55]/45,X[27]/47,X,psu idic(X)(p11.21)×2[5]/46,XX[13]. CMA has yielded a result of arr[GRCh37] Xp22.33p11.21(168552_55585678)×1[0.67],Xp11.21q28(55703291_155233098)×3[0.5]. CONCLUSION Karyotypes of Turner syndrome are complex and diverse, and a rare 46,X,psu idic(X)(p11.21)[55]/45,X[27]/47,X,psu idic(X)(p11.21)×2[5]/46,XX[13] mosaic karyotype with double pseudo-isodicentric X chromosome has been identified. Literature review suggested that this karyotype may lead to phenotypic diversification and a risk of reduced sensitivity to hormone therapy.
Humans ; Turner Syndrome/diagnosis* ; Female ; Pregnancy ; Chromosomes, Human, X/genetics* ; Mosaicism ; Prenatal Diagnosis ; Karyotyping ; Adult ; Karyotype ; Amniocentesis

Long non-coding RNAs (lncRNAs) reportedly function as important modulators of gene regulation and malignant processes in the development of human cancers. The lncRNA JPX is a novel molecular switch for X chromosome inactivation and differentially expressed JPX has exhibited certain clinical correlations in several cancers. Notably, JPX participates in cancer growth, metastasis, and chemoresistance, by acting as a competing endogenous RNA for microRNA, interacting with proteins, and regulating some specific signaling pathways. Moreover, JPX may serve as a potential biomarker and therapeutic target for the diagnosis, prognosis, and treatment of cancer. The present article summarizes our current understanding of the structure, expression, and function of JPX in malignant cancer processes and discusses its molecular mechanisms and potential applications in cancer biology and medicine.
Humans ; RNA, Long Noncoding/genetics* ; Neoplasms/genetics* ; MicroRNAs/genetics* ; Gene Expression Regulation ; X Chromosome Inactivation

OBJECTIVE: To carry out prenatal diagnosis and genetic analysis for a fetus with disorders of sex development (DSDs). METHODS: A fetus with DSDs who was identified at the Shenzhen People's Hospital in September 2021 was selected as the study subject. Combined molecular genetic techniques including quantitative fluorescence PCR (QF-PCR), multiplex ligation-dependent probe amplification (MLPA), chromosomal microarray analysis (CMA), quantitative real-time PCR (qPCR), as well as cytogenetic techniques such as karyotyping analysis and fluorescence in situ hybridization (FISH) were applied. Ultrasonography was used to observe the phenotype of sex development. RESULTS: Molecular genetic testing suggested that the fetus had mosaicism of Yq11.222qter deletion and X monosomy. Combined with the result of cytogenetic testing, its karyotype was determined as mos 45,X[34]/46,X,del(Y)(q11.222)[61]/47,X,del(Y)(q11.222),del(Y)(q11.222)[5]. Ultrasound examination suggested hypospadia, which was confirmed after elective abortion. Combined the results of genetic testing and phenotypic analysis, the fetus was ultimately diagnosed with DSDs. CONCLUSION This study has applied a variety of genetic techniques and ultrasonography to diagnose a fetus with DSDs with a complex karyotype.
Prenatal Diagnosis ; Mosaicism ; Chromosomes, Human, X ; Chromosomes, Human, Y ; Humans ; Male

OBJECTIVE: To investigate the clinical features and genetic etiology of a case of Turner syndrome (TS) with rapidly progressive puberty. METHODS: A child who had presented at the Pediatric Endocrinology Clinic of the Shenzhen People's Hospital on January 19, 2022 was selected as the study subject. Clinical data of the child were collected. Peripheral blood sample of the child was subjected to chromosomal microarray analysis (CMA) and multiple ligation-dependent probe amplification (MLPA). Previous studies related to TS with rapidly progressive puberty were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases with Turner syndrome and rapidly progressive puberty as the keywords. The duration for literature retrieval was set from November 9, 2021 to May 31, 2022. The clinical characteristics and karyotypes of the children were summarized. RESULTS: The child was a 13-year-and-2-month-old female. She was found to have breast development at 9, short stature at 10, and menarche at 11. At 13, she was found to have a 46,X,i(X)(q10) karyotype. At the time of admission, she had a height of 143.5 cm (< P3), with 6 ~ 8 nevi over her face and right clavicle. She also had bilateral simian creases but no saddle nasal bridge, neck webbing, cubitus valgus, shield chest or widened breast distance. She had menstruated for over 2 years, and her bone age has reached 15.6 years. CMA revealed that she had a 58.06 Mb deletion in the Xp22.33p11.1 region and a 94.49 Mb duplication in the Xp11.1q28 region. MLPA has confirmed monosomy Xp and trisomy Xq. A total of 13 reports were retrieved from the CNKI, Wanfang Data Knowledge Service Platform, Boku, CBMdisc and PubMed databases, which had included 14 similar cases. Analysis of the 15 children suggested that their main clinical manifestations have included short stature and growth retardation, and their chromosomal karyotypes were mainly mosaicisms. CONCLUSION The main clinical manifestations of TS with rapidly progressive puberty are short stature and growth retardation. Deletion in the Xp22.33p11.1 and duplication in the Xp11.1q28 probably underlay the TS with rapid progression in this child, which has provided a reference for clinical diagnosis and genetic counselling for her.
Humans ; Female ; Adolescent ; Puberty ; Turner Syndrome/genetics* ; Chromosomes, Human, X ; Karyotyping

Klinefelter syndrome (KS) is the most common genetic cause of human male infertility. However, the effect of the extra X chromosome on different testicular cell types remains poorly understood. Here, we profiled testicular single-cell transcriptomes from three KS patients and normal karyotype control individuals. Among the different somatic cells, Sertoli cells showed the greatest transcriptome changes in KS patients. Further analysis showed that X-inactive-specific transcript ( XIST ), a key factor that inactivates one X chromosome in female mammals, was widely expressed in each testicular somatic cell type but not in Sertoli cells. The loss of XIST in Sertoli cells leads to an increased level of X chromosome genes, and further disrupts their transcription pattern and cellular function. This phenomenon was not detected in other somatic cells such as Leydig cells and vascular endothelial cells. These results proposed a new mechanism to explain why testicular atrophy in KS patients is heterogeneous with loss of seminiferous tubules but interstitial hyperplasia. Our study provides a theoretical basis for subsequent research and related treatment of KS by identifying Sertoli cell-specific X chromosome inactivation failure.
Animals ; Humans ; Male ; Female ; Sertoli Cells/metabolism* ; Klinefelter Syndrome/genetics* ; Endothelial Cells ; Testis/metabolism* ; X Chromosome/metabolism* ; Mammals/genetics*

OBJECTIVE: To explore the etiology of a patient with Kallmann syndrome (congenital hypogonadism and anosmia) and a 45,X/46,XY karyotype. METHODS: Peripheral venous blood samples were collected from the proband and his parents and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The proband was found to harbor compound heterozygous variants of the PROKR2 gene, namely c.533G>C (p.W178S) and c.308C>T (p.A103V), which were inherited from his father and mother, respectively. The two variants were respectively predicted to be likely pathogenic and variant of unknown significance, respectively. CONCLUSION The reduced chromosomal mosaicism might have caused no particular clinical manifestations in this patient. For patients with features of Kallmann syndrome, genetic testing is conducive to early diagnosis and can provide a basis for genetic counseling and clinical treatment.
Humans ; Genetic Testing ; Hypogonadism/genetics* ; Kallmann Syndrome/genetics* ; Karyotype ; Mutation ; Exome Sequencing ; Chromosomes, Human, X/genetics* ; Chromosomes, Human, Y/genetics*

OBJECTIVES: To study the genetic polymorphism and population genetic parameters of 16 X-STR loci in Xinjiang Uygur population. METHODS: The Goldeneye^® DNA identification system 17X was used to amplify 16 X-STR loci in 502 unrelated individuals (251 females and 251 males). The amplified products were detected by 3130xl genetic analyzer. Allele frequencies and population genetic parameters were analyzed statistically. The genetic distances between Uygur and other 8 populations were calculated. Multidimensional scaling and phylogenetic tree were constructed based on genetic distance. RESULTS: In the 16 X-STR loci, a total of 67 alleles were detected in 502 Xinjiang Uygur unrelated individuals. The allele frequencies ranged from 0.001 3 to 0.572 4. PIC ranged from 0.568 8 to 0.855 3. The cumulative discrimination power in females and males were 0.999 999 999 999 999 and 0.999 999 999 743 071, respectively. The cumulative mean paternity exclusion chance in trios and in duos were 0.999 999 997 791 859 and 0.999 998 989 000 730, respectively. The genetic distance between Uygur population and Kazakh population was closer, and the genetic distance between Uygur and Han population was farther. CONCLUSIONS The 16 X-STR loci are highly polymorphic and suitable for identification in Uygur population, which can provide a powerful supplement for the study of individual identification, paternity identification and population genetics.
Female ; Humans ; Male ; DNA, Ribosomal ; Ethnicity/genetics* ; Gene Frequency ; Paternity ; Phylogeny ; Polymorphism, Genetic ; Microsatellite Repeats ; Chromosomes, Human, X/genetics*

OBJECTIVE: To explore the genetic basis for a child with febrile seizures. METHODS: Peripheral venous blood samples were taken from the child and his parents for the analysis of chromosomal karyotype and dynamic variant of the FMR1 gene. The family trio was also subjected to target capture and next generation sequencing (NGS) with a gene panel related to developmental retardation, mental retardation, language retardation, epilepsy and special facial features. RESULTS: The child was found to have a normal karyotype by conventional cytogenetic analysis (400 bands). No abnormal expansion was found with the CGG repeats of the FMR1 gene. NGS revealed that the child has carried a heterozygous c.864+1 delG variant of the MEF2C gene, which may lead to abnormal splicing and affect its protein function. The same variant was found in neither parent, suggesting that it has a de novo origin. Based on the American College of Medical Genetics and Genomics standards and guidelines, c.864+1delG variant of MEF2C gene was predicted to be pathogenic (PVS1+PS2+PM2). CONCLUSION MEF2C, as the key gene for chromosome 5q14.3 deletion syndrome which was speculated as a cause for febrile seizures, has an autosomal dominant effect. The c.864+1delG variant of the MEF2C gene may account for the febrile seizures in this patient.
Child ; Chromosome Deletion ; Chromosome Disorders ; Epilepsy ; Fragile X Mental Retardation Protein ; Humans ; Intellectual Disability/genetics* ; Karyotyping ; MEF2 Transcription Factors/genetics*