OBJECTIVE: To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family. METHODS: Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009). RESULTS: CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent. CONCLUSION This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Duplication/genetics* ; Male ; Pedigree ; DiGeorge Syndrome/diagnosis* ; Adult ; Chromosomes, Human, Pair 22/genetics* ; Abnormalities, Multiple

OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of seven pediatric patients with Acute myeloid leukemia (AML) positive for the t(16;21)(p11;q22) FUS::ERG fusion gene. METHODS: A retrospective analysis was carried out on the clinical data, treatment, and prognosis of seven AML patients with t(16;21)(p11;q22) FUS::ERG fusion gene admitted to Henan Children's Hospital between June 2015 and November 2024. Relevant literature was also reviewed. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-102-001). RESULTS: Among 297 pediatric patients with AML, 7 cases (2.36%) were positive for the t(16;21)(p11;q22) FUS::ERG fusion gene, including 3 males and 4 females, with a median age of 11 years (range: 3 ~ 12 years). According to the FAB classification, these included 1 case of M2, 3 cases of M5, and 3 cases of AML-not otherwise specified (non-M3). All 7 patients were found to harbor the t(16;21)(p11;q22) translocation, with 3 cases showing additional chromosomal abnormalities. Immunophenotyping revealed universal expression of CD13, CD33, CD34, and CD117, with partial expression of CD56, CD4, CD64, CD123, CD15, CD38, CD11b, HLA-DR, cMPO, and CD16. One patient achieved complete remission (CR) after the first course of DAE (cytarabine + daunorubicin + etoposide) induction chemotherapy but relapsed and discontinued the treatment. Six patients received DAH (cytarabine + daunorubicin + homoharringtonine) induction therapy, of whom 2 achieved CR after two courses and underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), resulting in an overall CR rate of 42.86%. Five children did not receive allo-HSCT and had a median overall survival of 9 months (range: 6 ~ 18 months). Two children who underwent transplantation achieved bone marrow morphological and molecular biological relapse at 6 and 9 months post-transplantation, respectively. After receiving combined chemotherapy and donor lymphocyte infusion, one child failed to achieve remission and died at 22 months post-transplantation, while the other has been followed up to date with positive fusion gene status. Their overall survival was 25 months and 30 months, respectively. CONCLUSION The t(16;21)(p11;q22) FUS::ERG fusion gene is rare in pediatric AML and associated with poor prognosis. Allo-HSCT may mitigate the adverse prognostic impact of the FUS::ERG fusion gene and contribute to prolonged survival.
Humans ; Male ; Child ; Female ; Leukemia, Myeloid, Acute/drug therapy* ; Oncogene Proteins, Fusion/genetics* ; Translocation, Genetic ; Retrospective Studies ; RNA-Binding Protein FUS/genetics* ; Chromosomes, Human, Pair 16/genetics* ; Adolescent ; Child, Preschool ; Chromosomes, Human, Pair 21/genetics* ; Prognosis ; Treatment Outcome

OBJECTIVE: To investigate the genetic mechanism for adverse pregnancies due to submicroscopic chromosomal structural variants in two cases, and to provide a precise guidance for preimplantation genetic testing. METHODS: Two families who had visited Chengdu Women's and Children's Central Hospital for reproduction guidance due to recurrent miscarriages, adverse pregnancy history and abnormal genetic testing of the offspring in June and December 2023 were selected as the study subjects. Chromosomal karyotyping and optical genome mapping (OGM) were carried out on peripheral blood samples from the two couples, and preimplantation genetic testing for structural rearrangement (PGT-SR) were performed on the blastocyst trophoblasts. This study was approved by the Medical Ethics Committee of the Hospital (Ethic No.: 2023-23). RESULTS: No abnormality was found on the G-banded karyotyping analysis for both couples. The OGM results revealed that the female partner of couple 1 had a translocation between 4pter-p16.3 (3.99 Mb) and 11pter-p15.4 (2.66 Mb), whilst no abnormality was found in the male partner. Similarly, the male partner of couple 2 had a translocation between 19q13.43-qter (1.90 Mb) and 22q13.31-qter (3.34 Mb). No abnormality was found in the female partner of couple 2. Neither breakpoints nor the adjacent region had involved an OMIM gene, except the formation of a fusion gene ZIM2-AS1-Z82186.1 (Both genes are non-coding, and the fusion gene was deemed as variant of unknown significance). PGT-SR of 11 blastocysts derived from couple 1 revealed that one embryo was suitable for priority transfer, three embryos were suitable for transfer, one embryo was recommended for genetic counselling, and six embryos were unsuitable for the transfer. For couple 2, six blastocysts were tested, of which only one embryo was deemed suitable for transfer. CONCLUSION When genetic testing of offspring indicates copy number variations such as deletions, duplications or mosaicism, the high-resolution OGM technique can be selected to screen parents for submicroscopic chromosomal structural variations. The result can facilitate accurate assessment for the risk of recurrence in offspring, selection of suitable method for reproduction, and identifying targets for PGT.
Humans ; Female ; Pregnancy ; Adult ; Male ; Karyotyping ; Chromosome Aberrations ; Abortion, Habitual/genetics* ; Preimplantation Diagnosis ; Genetic Testing

OBJECTIVE: To explore the application value of artificial intelligence (AI)-assisted chromosomal karyotype analysis in the diagnosis of prenatal chromosomal mosaicism. METHODS: A retrospective analysis was conducted on 172 pregnant women who underwent amniocentesis at the Department of Medical Genetics and Prenatal Diagnosis, the Third Affiliated Hospital of Zhengzhou University between January 2019 and December 2024. All cases whose fetuses were diagnosed with chromosomal mosaicism via karyotype analysis and stratified into two groups based on the analytical software employed: the conventional analysis group (n = 70), which utilized Leica analysis software for karyotype image recognition and cell counting; and the AI-assisted analysis group (n = 102), which utilized AI-assisted software for the same procedures. The clinical performance of AI-assisted karyotype analysis in diagnosing chromosomal mosaicism was comprehensively evaluated by comparing the types of mosaic karyotypes, distribution of mosaic ratios, and verification outcomes of different detection modalities between the two groups. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-406-01). RESULTS: No statistically significant difference was observed in baseline characteristics (maternal age, gestational week, and indications for prenatal diagnosis) between the two groups. Regarding the detection efficacy for numerical and structural mosaicisms, no significant difference was found in the detection of numerical mosaicism. However, the conventional analysis group exhibited a significantly higher detection rate of autosomal structural mosaicism compared to the AI-assisted group (11.43% vs. 0.98%, P < 0.05). Numerical mosaicism cases were further verified using copy number variation sequencing (CNV-seq) and/or fluorescence in situ hybridization (FISH). The AI-assisted group demonstrated a significantly lower inconsistency rate (5.56% vs. 20.41%, P < 0.05) compared to the conventional group. For low-proportion (< 10%) chromosomal mosaicism, the AI-assisted group had a significantly lower detection rate (13.25% vs. 29.69%, P < 0.05). Subsequent validation of low-proportion mosaicism by CNV-seq and/or FISH showed a higher consistency rate in the AI-assisted group (81.82% vs. 54.55%), though the difference did not reach statistical significance (P = 0.360). CONCLUSION For the karyotyping analysis of prenatal chromosomal mosaicism, AI-assisted karyotype analysis shows high accuracy and consistency in identifying numerical chromosomal mosaicism, particularly in reducing the detection of low-proportion (< 10%) mosaicism while improving verification accuracy. AI-assisted analysis can significantly improve the detection accuracy of numerical mosaicism and mitigate the risk of misclassification for low-proportion (< 10%) mosaicism, thereby providing more precise clinical evidence for the prenatal diagnosis of chromosomal mosaicisms.
Humans ; Female ; Mosaicism ; Pregnancy ; Karyotyping/methods* ; Artificial Intelligence ; Prenatal Diagnosis/methods* ; Adult ; Retrospective Studies ; Chromosome Disorders/genetics* ; Amniocentesis

OBJECTIVE: To analyze the clinical characteristics of patients with 11q23 rearrangement acute lymphoblastic leukemia (ALL) with non-KMT2A::AFF1 fusion genes. METHODS: The clinical data of 10 patients with KMT2A fusion gene positive and partner gene non-AFF1 ALL admitted to Henan Cancer Hospital from December 2016 to December 2024 were retrospectively summarized. The immunophenotype, molecular genetic characteristics, clinical manifestations and disease prognosis of these patients were analyzed. This research has been approved by the Medical Ethics Committee of Henan Cancer Hospital (Ethics No.: 2019342). RESULTS: Among the 10 patients, the fusion genes were KMT2A::MLLT1 in 7 cases, KMT2A::MLLT4, KMT2A::MLLT3 and KMT2A::MLLT10 in 1 case each. The European Group for the Immunological Classification of Leukemias (EGIL) classification included 6 cases of T-ALL, 2 cases of pro-B-ALL, 1 case of Common-B-ALL and 1 case of pre-B-ALL. 4 cases of B-ALL all expressed CD19, cCD79a, CD38 and HLA-DR, and some expressed CD34 and CD22, without expression or weak expression of CD10, without expression of CD20. One case was accompanied by myeloid marker CD15 expression. 6 cases of T-ALL all expressed CD34, CD7, most expressed CD38, and some expressed CD3, CD5, CD2, CD4 and CD8, and 1 case expressed CD4 and CD8 together. Chromosomal abnormalities were detected in 3 cases, 5 cases were positive for WT1 fusion gene, and 6 cases had gene alterations. 9 patients achieved the first complete remission (CR1) during chemotherapy, and 1 patient relapsed within 6 months after CR1. At the last follow up, 1 patient (the fusion gene was KMT2A::MLLT4) remained unrelieved. There were 2 cases of KMT2A rearrangement (KMT2A-r) persistent positive (+/+) and 8 cases of KMT2A-r negative (+/-). The overall survival (OS) rate and leukemia-free survival (LFS) rate of patients with KMT2A-r persistent positive were significantly lower than those of patients with negative change, and the differences were statistically significant (P values were all < 0.05). Among the 3 patients who received chemotherapy+allogeneic hematopoietic stem cell transplantation (allo-HSCT), no relapse was observed until the follow up day. The OS rate and LFS rate of patients with KMT2A::MLLT1 and chemotherapy+allo-HSCT were higher than those of non-KMT2A::MLLT1 and single chemotherapy patients, and the differences were not statistically significant (P values were all ≥ 0.05). There was no significant difference in OS rate and LFS rate between T-ALL and B-ALL patients (P values were all ≥ 0.05). The median LFS time of the 10 patients was 32 (0 ~ 100) months, and the median OS time was 36 (1 ~ 101) months. CONCLUSION The 11q23 rearrangement ALL with non-KMT2A::AFF1 transcript is mainly KMT2A::MLLT1, T-ALL is more common, and the rate of chromosomal karyotype detection is relatively low. Persistent positive KMT2A-r is unfavorable for patient survival, and allo-HSCT during the CR1 period may improve patient survival.
Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Female ; Male ; Myeloid-Lymphoid Leukemia Protein/genetics* ; Histone-Lysine N-Methyltransferase/genetics* ; Adult ; Adolescent ; Chromosomes, Human, Pair 11/genetics* ; Child ; Transcriptional Elongation Factors/genetics* ; Gene Rearrangement ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies ; Young Adult ; Middle Aged ; Prognosis ; Child, Preschool ; DNA-Binding Proteins/genetics*

OBJECTIVE: To explore the clinical significance of trisomy 7 signaled by non-invasive prenatal testing (NIPT). METHODS: Pregnant women with high risk for trisomy 7 by NIPT from January 2017 to December 2023 were selected as the study subjects, and the results of prenatal diagnosis and follow-up were analyzed. Literature related to pregnant women with a high risk for trisomy 7 by NIPT from January 2016 to July 2024 was retrieved from China Biomedical Literature Database, Wanfang Database, China National Knowledge Infrastructure and PubMed database. Relevant information such as the incidence of trisomy 7 by NIPT, positive predictive value (PPV), and pregnancy outcomes were collected. This study has been approved by the Medical Ethics Committee of Lianyungang Maternal and Child Health Care Hospital (Ethics No. JS2022010). RESULTS: A total of 51 women with a high risk for trisomy 7 by NIPT were identified. Thirty-two of them had chosen chromosomal microarray analysis (CMA) of amniotic fluid cells, and 1 case of mosaic trisomy 7 was detected, which had yielded a PPV of 3.13%. Four women had opted termination of pregnancy, 1 had miscarriage, 4 had pre-term and/or low weight birth, whilst the remaining 42 (82.4%) had full-term delivery. In total 19 literature were retrieved, which had involved 278 cases of trisomy 7 signaled by NIPT, among which 5 fetuses with mosaic trisomy 7 (3.14%) were confirmed. Among the 211 women with follow-up outcomes, 2 (0.95%) had intrauterine growth restriction, 3 (1.42%) had abnormal fetal structure detected by ultrasound, 2 (0.95%) had miscarriage, 9 (4.27%) underwent pregnancy termination, 28 (13.27%) had preterm and/or low weight birth, whilst 167 (79.14%) had normal delivery. In 18 cases, chromosomal analysis of placental tissue was carried out, and 17 were confirmed to have mosaicism trisomy 7. CONCLUSION The PPV for trisomy 7 signaled by NIPT is extremely low. Although most of such women had a full term delivery, adverse pregnancy outcomes may still occur in a minority of cases. Clinicians should provide adequate genetic counseling for such women and recommend appropriate prenatal diagnosis strategies and optimal perinatal management plans.
Humans ; Female ; Pregnancy ; Trisomy/diagnosis* ; Chromosomes, Human, Pair 7/genetics* ; Adult ; Prenatal Diagnosis/methods* ; Noninvasive Prenatal Testing/methods* ; Pregnancy Outcome ; Clinical Relevance

OBJECTIVE: To explore the clinical phenotype, pregnancy outcome and follow-up of fetuses with 15q11.2BP1-BP2 microdeletions in order to provide a basis for prenatal and reproductive consultation. METHODS: From March 2019 to December 2023, 20 fetuses who were diagnosed with 15q11.2BP1-BP2 microdeletion syndrome at the Prenatal Diagnosis Center of General Hospital of Ningxia Medical University were selected as the study subjects. Results of genetic testing and ultrasound examination, outcome of pregnancy, and postnatal follow-up were retrospectively analyzed. This study has been approved by the Ethics Committee of General Hospital of Ningxia Medical University ([2020]0520B). RESULTS: None of the 20 fetuses was found to have chromosomal abnormality, whilst all were found to harbor a 15q11.2 BP1-BP2 microdeletion by low-depth whole genome sequencing (CNV-seq). The range of deletions was determined as 0.26 ~ 0.87 Mb, and all were rated as pathogenic CNVs. Three fetuses had abnormal ultrasound findings, including 1 with widened renal pelvis, 1 with agenesis of corpus callosum, and 1 with nuchal fold thickening. Parental verification in 10 couples verified that two fetal deletions were de novo, whilst the remaining eight were inherited from a phenotypically normal parent. Following genetic counseling, three couples had opted to terminate the pregnancy, whilst the remaining 17 had continued with the pregnancy until delivery. The 17 liveborns were followed up for 2 months to 5 years, with no obvious abnormality in growth and development noted. CONCLUSION CNV-seq plays an important role in the prenatal diagnosis of 15q11.2 BP1-BP2 microdeletions. Such deletions may not always lead to disease phenotypes. Individualized consultation and long-term follow-up, in combination with intrauterine ultrasound and parental verification are necessary.
Humans ; Female ; Pregnancy ; Chromosomes, Human, Pair 15/genetics* ; Genetic Counseling ; Prenatal Diagnosis ; Chromosome Deletion ; Adult ; Fetus/abnormalities* ; Retrospective Studies ; Pregnancy Outcome ; Ultrasonography, Prenatal ; Genetic Testing ; DiGeorge Syndrome/diagnosis* ; Male

OBJECTIVE: To explore the genetic characteristics of a Chinese pedigree with rare mosaic 11q partial duplication and its pathogenetic mechanisms. METHODS: A pedigree which underwent prenatal diagnosis at Wenzhou Central Hospital between September 25, 2015 and November 30, 2023 was selected for the study. Clinical data were collected from the pedigree. Peripheral blood samples from the parents, amniotic fluid from the fetus, and peripheral blood sample from the neonate were obtained. Genetic testing was carried out by using G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) technology. Relevant literature was searched in the CNKI, Wanfang Data Knowledge Service Platform, and PubMed databases to summarize the clinical phenotypes of patients with 11q partial duplication. This study was approved by the Medical Ethics Committee of Wenzhou Central Hospital (Ethics No. L2024-07-080). RESULTS: The pregnant woman (G₃) had a history of adverse pregnancy outcomes. During her first pregnancy (G₁), prenatal ultrasound indicated intrauterine growth restriction and a Dandy-Walker variant. Follow-up at 8 years of age showed developmental delays and mild intellectual disability. During her second pregnancy (G₂), prenatal ultrasound revealed nasal bone hypoplasia, and the pregnancy was terminated at 23rd gestational week. During her third pregnancy (G₃), all prenatal tests were normal, and the neonate showed normal growth and development at 4 months of age. The karyotype of amniotic fluid of her first pregnancy was 46,X?, and the SNP-array analysis of neonatal peripheral blood showed arr[GRCh37/hg19]11q13.4q25(70432450_134607121)×2~3, with a mosaicism rate being approximately 40%. The karyotype for her second pregnancy was 46,X?,rec(11)dup(11q)inv(11)(p15q13)dmat[6]/46,X?[27], and the SNP-array result was arr[GRCh38]11q13.4q25(71406636_135067522)×2~3, with a mosaicism rate being approximately 75%. The karyotype for her third pregnancy was 46,X?,inv(11)(p15q13)mat, and the SNP-array result was arr(XN)×1,(1~22)×2. The karyotype of the woman was 46,XX,inv(11)(p15q13), and that of her husband was 46,XY. A review of 12 similar cases (including G₁) from the literature revealed that the common clinical phenotypes of 11q partial duplication included intellectual disability (12/12), developmental delay (12/12), ear abnormalities (12/12), microcephaly (10/12), seizures (8/12), hypotonia (8/12), and congenital heart malformations (7/12). CONCLUSION Mosaic partial duplication of 11q may underlie the genetic etiology of this pedigree. The pregnant woman is a carrier of an inversion on chromosome 11, which might have formed the mosaic 11q partial duplication through meiotic errors and mitotic trisomy rescue mechanisms during reproduction.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Chromosome Duplication ; Chromosomes, Human, Pair 11/genetics* ; East Asian People/genetics* ; Karyotyping ; Mosaicism ; Pedigree ; Polymorphism, Single Nucleotide ; Prenatal Diagnosis

OBJECTIVE: To analyze the chromosome status of pre-implantation embryos from women of different ages, and assess the impact of age on it. METHODS: A retrospective analysis was carried out on the results of PGT-A and PGT-M+PGT-A cycles by whole-genome amplification followed by next generation sequencing at the Second People's Hospital of Nanning between July 2021 and November 2023. The embryos were divided into five groups based on the women's age: ≤ 30 years old group, 31 ~ 34 years old group, 35 ~ 37 years old group, 38 ~ 40 years old group, and ≥ 41 years old group.The chromosomal status of embryos for each group was compared. This study has been approved by the Ethic Committee of the Hospital (Ethics No. Y2024312A). RESULTS: This study has involved 390 couples and 436 PGT cycles, with a total of 1 651 blastocysts biopsied and analyzed. Among these, 835 embryos (50.6%) were found to have chromosomal abnormalities, including 490 (29.7%) with aneuploidies, 154 (9.3%) with chromosomal segment abnormalities, and 264 (16.0%) with chromosome mosaicisms. After adjusting the dosages of Gn, female BMI, male age, PGT indications, infertility type, LH, AMH and other parameters, maternal age appeared to be an independent factor for chromosomal abnormalities and aneuploidies in blastocysts (OR = 1.132, 95%CI = 1.089-1.177, P < 0.001; OR = 1.250, 95%CI = 1.188-1.315, P < 0.001). With the increase in female age, embryonic chromosome abnormalities have significantly increased in each group, with the rates being 32.3% (126/390), 43.1% (189/439), 45.1% (116/257), 66.3% (250/377), and 81.9% (154/188) (P < 0.001). Chromosomal aneuploidies have also significantly increased, with the rates being 8.2% (32/390), 16.6% (73/439), 24.5% (63/257), 49.6% (187/377), and 71.8% (135/188) (P < 0.001). The proportion of embryos with ≥ 2 chromosome abnormalities also significantly increased in abnormal embryos, with the rates being 28.6% (36/126), 30.2% (57/189), 39.7% (46/116), 48.4% (121/250), and 64.9% (100/154) (P < 0.001). Of note, the female age did not affect the prevalence of chromosomal segment abnormalities and mosaicisms (all P > 0.05). CONCLUSION Above findings suggested that along with the increase in female age, there is an increase in the rate and complexity of chromosomal abnormalities, which may contribute to infertility in women with elder age.
Humans ; Female ; Maternal Age ; Adult ; Retrospective Studies ; Chromosome Aberrations ; Preimplantation Diagnosis/methods* ; Pregnancy ; Blastocyst/metabolism* ; Aneuploidy ; Fertilization in Vitro ; Male

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