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

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 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*

OBJECTIVE: To explore the genetic basis for a child featuring short stature, saddle nose, cryptorchidism and mental retardation. METHODS: The child and his parents were subjected to G-banded karyotyping and chromosomal microarray analysis (CMA). RESULTS: The child was found to have a 46,Y,der(X)t(X;Y)(p22;q11)mat karyotype. CMA has revealed a 8.3 Mb deletion at Xp22.33p22.31 and a 43.3 Mb duplication at Yq11.221qter. His mother had a karyotype of 46,X,der(X)t(X;Y)(p22;q11). His father had a normal karyotype. CONCLUSION The child has carried an unbalanced translocation der(X)t(X;Y) (p22;q11) derived from his mother. His clinical phenotype has correlated with the size and position of X chromosome deletion. Compared with the females, abnormal phenotypes such as mental retardation and growth retardation of male carriers are more severe.
Child ; Chromosome Banding ; Chromosomes, Human, X/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Translocation, Genetic

OBJECTIVE: To analyze the clinical symptom and parental origin of patients with MECP2 duplication syndrome in order to provide a basis for genetic counseling and prenatal diagnosis. METHODS: Clinical symptoms of four patients who were diagnosed with MECP2 duplication syndrome by copy number variation sequencing (CNV-Seq) were reviewed. The maternal origin of the duplications were verified. RESULTS: All patients were males, and CNV-Seq revealed that they have all harbored a duplication in the Xq28 region spanning 0.32 ~ 0.86 Mb, which were derived from asymptomatic mothers. The clinical symptoms of three patients with three copies included delayed speech, intellectual disability, and muscular hypotonia, while the patient with four copies had died at 6 months after birth, with clinical symptoms including recurrent infections, seizures, and spasticity. CONCLUSION The four cases of MECP2 duplication syndrome have shown complete penetrance and have all derived from asymptomatic mothers. As a stable and reliable method, CNV-Seq can accurately detect the MECP2 duplication syndrome.
Chromosomes, Human, X ; DNA Copy Number Variations ; Gene Duplication ; Humans ; Male ; Mental Retardation, X-Linked ; Methyl-CpG-Binding Protein 2/genetics* ; Phenotype

OBJECTIVE: To explore the pathogenesis and genetic characteristics of a fetus with a der(X)t(X;Y)(p22.3;q11.2) karyotype. METHODS: G-banding karyotyping analysis, BoBs (BACs-on-Beads) assay, and single nucleotide polymorphism array (SNP-array) were used to delineate the structural chromosomal aberration of the fetus. The parents of the fetus were also subjected to karyotyping analysis. RESULTS: The fetus and its mother were both found to have a karyotype of 46,X,add(X)(p22), while the father was normal. BoBs assay indicated that there was a lack of Xp22 but a gain of Yq11 signal. SNP-array confirmed that the fetus and its mother both had a 7.13 Mb deletion at Xp22.33p22.31 (608 021-7 736 547) and gain of a 12.52 Mb fragment at Yq11.221q11.23 (16 271 151-28 788 643). CONCLUSION The fetus was determined to have a karyotype of 46,X,der(X)t(X;Y)(p22.3;q11.2)mat. The combined use of various methods has facilitated delineation of the fetal chromosomal aberration and prediction of the risk prediction for subsequent pregnancy.
Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, X/genetics* ; Chromosomes, Human, Y/genetics* ; Female ; Fetus ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic

With the application of BACs-on-Beads (BoBs) and array-comparative genome hybridization (aCGH) technologies in prenatal diagnosis, microdeletion/microduplications at Xp22.3 have been frequently detected. However, the relatively high prevalence and lack of knowledge of such disorders have brought difficulties for clinical genetic counseling. Here, recent progress of research on microdeletion/microduplications at Xp22.3, including epidemiology, pathogenesis, clinical manifestation, and prenatal diagnosis, is reviewed.
Chromosomes, Human, X ; genetics ; Comparative Genomic Hybridization ; Female ; Genetic Counseling ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Research ; trends

OBJECTIVE: To explore the genetic basis for a fetus with cleft lip and palate. METHODS: Copy number variations (CNVs) in the fetus and his parents were detected with chromosomal microarray analysis (CMA). RESULTS: As revealed by the CMA assay, the fetus has carried a 228 kb deletion in Xp11.22 region and a 721 kb duplication in 9p21.1. Both CNVs were inherited from the parents. The CNV in Xp11.22 was predicted to be pathogenic by involving the PHF8 gene, whilst the CNV in 9p21.1 was predicted to be benign. CONCLUSION Deletion of the Xp11.22 region probably underlies the cleft lip and palate in this fetus.
Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Cleft Lip ; diagnosis ; genetics ; Cleft Palate ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Fetus ; Histone Demethylases ; Humans ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; Transcription Factors

OBJECTIVE: X-linked adrenoleukodystrophy (ALD) is a severe inherited disorder leading to rapid neurological deterioration and premature death. Allogeneic hematopoietic stem cell transplantation (HSCT) is still the only treatment that halts the neurologic symptoms in ALD. However, many patients lack suitable human leukocyte antigen (HLA) matched related donors and must rely on alternative donors for a source of stem cells. The purpose of this study was to explore the outcomes of haploidentical allogeneic stem cell transplantation for ALD patients. METHODS: Between December 2014 and December 2018, eight children with ALD lacking HLA matched related or unrelated donors were treated with haploidentical allogeneic hematopoietic stem cell transplantation. The patients received conditioning regimen with busulfan 9.6 mg/kg, cyclophosphamide 200 mg/kg and fludarabine 90 mg/m². Graft-versus-host disease (GVHD) prophylaxis consisted of anti-human thymocyte globulin, cyclosporine A, mycophenolate mofetil and short course of methotrexate. RESULTS: All the 8 children received allogeneic stem cell transplants from their fathers. The median age of the recipients was 8 (range: 5-12) years. The median age of the donors was 36 (range: 32-40) years. All the recipients received granulocyte colony-stimulating factor (G-CSF) mobilized bone marrow and peripheral blood-derived stem cells. The median number of total mononuclear cells dose and CD34+ dose was 10.89 (range: 9.40-12.16)×10⁸/kg and 7.06 (range: 0.74-7.80)×10⁶/kg, respectively. Neutrophil engraftment occurred a median of 11 days (range:8-13 days) after transplantation. Platelet engraftment occurred a median of 10 days (range:8-12 days) after transplantation. All the patients achieved complete donor chimerism at the time of engraftment. Four patients had grades II-IV acute GVHD and 1 had chronic graft-versus-host disease. No severe chronic GVHD occurred. Among all the children, 2 had cytomegalovirus (CMV) DNAemia and 2 Epstein-Barr virus (EBV) DNAemia. Overall, seven of them survived and had no major complications related to transplantation. One died of cerebral hernia after epilepsy 125 days after transplantation. CONCLUSION The preliminary observation demonstrates that haploidentical allogeneic stem cell transplantation with this novel regimen could successfully achieve full donor chimerism in ALD patients. According to our experience, haploidentical allogeneic hematopoietic stem cell transplantation is safe and feasible in the treatment of X-linked adrenoleukodystrophy.
Adrenoleukodystrophy/therapy* ; Adult ; Bone Marrow Transplantation ; Child ; Child, Preschool ; Chromosomes, Human, X ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Transplantation Conditioning