OBJECTIVE: To summarize the clinical and genetic characteristics of a child with 46,XX Ovotesticular disorder of sex development (46,XX OTDSD) due to copy number variation of SOX3 gene. METHODS: A 46,XX male patient presented at the Capital Center for Children's Health, Capital Medical University in November 2024 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples were taken from the child and his parents and subjected to trio whole-genome sequencing. Skewed X-chromosome inactivation was tested in the child and his mother. A literature review was carried out on 46,XX males associated with mutations of the SOX3 gene. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: SHERLL2025056). RESULTS: The 10-year-old boy presented with hypospadias and cryptorchidism at birth. Chromosome analysis at one year and a half revealed a 46,XX karyotype. Gonadal biopsy showed testicular tissue, while ultrasound at the age of 10 detected ovotesticular tissue. Whole-genome sequencing identified a 660 kb duplication in the Xq27.1 region, which was derived from his mother. X-chromosome inactivation testing showed random inactivation in the child and mild non-random inactivation in the mother. Literature review has found 11 publications involving 15 patients (including our case), among whom 14 had a male social gender. They had primarily presented with hypospadias at birth but had no significant endocrine abnormalities. Most patients had experienced testicular failure after puberty. SOX3 related 46,XX males are mainly caused by de novo duplications, although a few maternal carriers had been discovered. CONCLUSION Duplication of the SOX3 gene probably underlay the pathogenesis is this 46,XX male. Individuals with 46,XX SRY negative male phenotypes should be routinely screened for SOX3 gene variants. Structural variations of the SOX3 gene can lead to complete or partial sex reversal in 46,XX individuals with minimal impact on intellectual and motor development, as well as other endocrine hormones.
Child ; Humans ; Male ; 46, XX Disorders of Sex Development/genetics* ; DNA Copy Number Variations ; Gene Duplication ; Phenotype ; SOXB1 Transcription Factors/genetics*

Humans ; Genetic Counseling ; Genetic Testing ; Disorders of Sex Development/therapy* ; Consensus ; Child ; Male ; Practice Guidelines as Topic ; Female ; Quality of Life

OBJECTIVE: To analyze the demographic and clinical characteristics of inpatients with osteoporotic vertebral compression fractures (OVCF) and provide a basis for clinical prevention and treatment. METHODS: A retrospective analysis was performed on the clinical data of 744 inpatients diagnosed with OVCF between January 2017 and December 2021 who met the inclusion criteria. Among them, 146 were male and 598 were female, with age ranging from 50 to 95 years (mean, 69.37 years). The demographic characteristics (gender, age, ethnicity, occupation, regional distribution, urban-rural distribution, and seasonal incidence) and clinical features [causes of injury, history of vertebral fractures, smoking and drinking history in males, comorbidities (hypertension, diabetes, coronary atherosclerotic heart disease, cerebral infarction), body mass index (BMI), blood lipid levels, menopausal age in females, vertebral bone mineral density T-value, number of vertebral fractures, and fracture segment distribution] of OVCF patients were analyzed. Multiple linear regression was used to analyze the independent risk factors of vertebral osteoporosis. RESULTS: The demographic analysis indicated that female patients with OVCF were significantly younger than male patients ( P<0.05). Significant differences were observed in the age distribution of OVCF between males and females ( P<0.05), with the highest proportion of male patients in the 70-79 years group (37.0%) and the highest proportion of female patients in the 60-69 years group (40.0%). From 2017 to 2021, the age of onset for OVCF gradually increased, with a similar trend observed for both genders. The distribution of occupations between genders also showed significant differences ( P<0.05); with the top three occupations for males being farmers (48.6%), retirees (24.7%), and workers (13.7%), while for females, the leading occupations were farmers (51.5%), retirees (19.4%), and service workers (10.0%). Female OVCF patients had higher BMI, vertebral bone mineral density T-value, history of vertebral fractures, hypertension prevalence, and blood lipid levels compared to male patients ( P<0.05). No significant difference between the males and the females was found in ethnicity, seasonal distribution, regional distribution, urban-rural distribution, causes of injury, number of vertebral fractures, or prevalence of comorbidities (except hypertension) ( P>0.05). Among the 744 OVCF patients, a total of 1 309 vertebrae were involved, with 628 thoracic vertebrae (48.0%) and 681 lumbar vertebrae (52.0%). The most common fracture segments were L ₁ (22.5%), T ₁₂ (21.2%), followed by L ₂ (12.2%) and T ₁₁ (10.2%). No significant gender difference was observed in the distribution of fracture segments ( P>0.05). Multiple linear regression analysis indicated that older age, female, and lower BMI were independent risk factors for vertebral osteoporosis ( P<0.05). CONCLUSION The age of onset of OVCF patients is increasing year by year. The number of fractured vertebral bodies, age distribution of morbidity, occupational distribution, BMI, history of vertebral fracture, hypertension, and blood lipid levels are related to gender. The occurrence of OVCF is mainly in the thoracolumbar segment. The female, older age, and lower BMI are independent risk factors of osteoporosis.
Humans ; Male ; Female ; Aged ; Middle Aged ; Retrospective Studies ; Spinal Fractures/etiology* ; Aged, 80 and over ; Osteoporotic Fractures/etiology* ; Fractures, Compression/etiology* ; Risk Factors ; Bone Density ; China/epidemiology* ; Osteoporosis/epidemiology* ; Comorbidity ; Inpatients ; Sex Factors ; Age Factors

OBJECTIVE: To analyze the current status and trends of the disease burden of knee osteoarthritis (KOA) in China from 1990 to 2023, and to examine the epidemiological characteristics of age, gender differences, and attribution to high body mass index (BMI), in order to provide a basis for formulating prevention and treatment strategies to reduce the disease burden of KOA in China. METHODS: Based on the 2023 Global Burden of Disease Study (GBD) database, data on the number, rate, and age-standardized rate of incidence, prevalence, disability-adjusted life years (DALYs) for KOA, and DALYs for KOA attributable to high BMI in the Chinese population from 1990 to 2023 were integrated. The Joinpoint 5.4.0.0 software was used to analyze the age and gender differences in KOA and the epidemiological characteristics attributable to high BMI. RESULTS: The standardized incidence, prevalence, and DALYs rates of KOA in China in 2023 increased by 6.46%, 6.43%, and 6.93%, respectively, compared with 1990. In terms of age, the disease burden of KOA in China was lowest in the age group of 30-34 years, with the highest incidence rate in the age group of 50-54 years, whereas the prevalence rate and DALYs rate continued to increase with age, and both were highest in the age group of ≥70 years. In terms of gender, all disease burden standardized rate indicators were higher in females than in males, and the difference widened with age. The rate of BMI-attributable DALYs increased at an annual average rate of 1.57% (95% CI: 1.55, 1.59) from 1990 to 2023, again with significant age and gender differences. CONCLUSION The continued growth of the KOA disease burden and significant population differences characterizing China call for focused attention on the female middle-aged and elderly population, enhanced weight management, and implementation of targeted preventive and control measures.
Humans ; Osteoarthritis, Knee/epidemiology* ; China/epidemiology* ; Male ; Female ; Middle Aged ; Incidence ; Aged ; Adult ; Prevalence ; Body Mass Index ; Disability-Adjusted Life Years ; Cost of Illness ; Aged, 80 and over ; Sex Factors ; Global Burden of Disease ; Age Factors ; Young Adult ; Quality-Adjusted Life Years

PURPOSE: Deep vein thrombosis (DVT) of the left and right lower extremities was treated in the same way, but the left and right extremities received different levels of attention. This study aimed to investigate the differences between the right and left lower extremity deep vein thrombosis (LEDVT). METHODS: Clinical characteristics of LEDVT patients from July 2020 to June 2022 were retrospectively analyzed to compare the incidence of LEDVT on different limbs, demographics, predisposing factors, and anatomical characteristics. The exclusion criteria were bilateral LEDVT and recurrent thrombosis. Measured data was analyzed using independent samples t-test or Mann-Whitney test. Count data were analyzed by Chi-square test. A p < 0.05 was considered a statistically significant difference. RESULTS: There were 478 patients included in this study and the ratio of left to right LEDVT on the left and right limbs was 3.16:1 (363:115). Left LEDVT predominantly affected female, with the major aged > 50 years (50 - 60 years: 16.80%; > 60 years: 57.30%). The primary predisposing factor was iliac vein compression syndrome, with iliofemoral thrombosis being the main type. Male patients with LEDVT on the right limb were predominant and the age of onset was usually ≤ 60 years (52.17%). The main predisposing factor was recent surgery or trauma (< 30 days) and femoropopliteal thrombosis was the main type. In more detail, the left iliac vein was compressed mainly in the proximal segment, and the right iliac vein was compressed mainly in the intermediate and distal segments. Recent surgery or trauma to the locomotor system and genitourinary system often induced LEDVT. CONCLUSION The incidence of LEDVT on the left is significantly higher than that on the right. LEDVT on different sides has different characteristics, which is crucial for prevention and diagnosis in the relevant population so there are also differences in treatment of the affected limbs.
Humans ; Venous Thrombosis/etiology* ; Male ; Female ; Middle Aged ; Lower Extremity/blood supply* ; Retrospective Studies ; Adult ; Aged ; Age Factors ; Sex Factors ; Risk Factors ; Acute Disease ; Incidence ; Aged, 80 and over ; Young Adult ; Adolescent

This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.
Humans ; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Disorder of Sex Development, 46,XY/blood* ; Male ; Membrane Proteins/genetics* ; Child, Preschool ; Child ; Retrospective Studies ; Adolescent ; Female ; Mutation ; Testosterone/blood* ; Infant ; Dihydrotestosterone/blood*

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

The patient, assigned female at birth and aged 1 year and 7 months, presented with clinical manifestations of 46,XY disorders of sex development. The external genitalia exhibited a severely undermasculinized phenotype. Laboratory tests and gonadal biopsy indicated poor Leydig cell function and good Sertoli cell function. Genetic testing revealed compound heterozygous mutations of c.867-2A>C and c.547G>A (p.G183R) in the LHCGR gene. The patient was ultimately diagnosed with type II Leydig cell hypoplasia. Type II Leydig cell hypoplasia presents a broad spectrum of clinical phenotypes, characterized by a lack of parallel function between Leydig cells and Sertoli cells, and significant individual variability in spermatogenesis and gender assignment. This condition should be considered when there is poor Leydig cell function but good development of Wolffian duct derivatives.
Female ; Humans ; Infant ; Disorder of Sex Development, 46,XY/genetics* ; Leydig Cells/pathology* ; Mutation ; Receptors, LH/genetics* ; Testis/abnormalities*

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, repetitive behaviors, and restricted interests. Studies have shown that it is more prevalent in males than females. Although this issue has attracted academic attention since the 20th century, the specific mechanisms underlying the gender differences in ASD remain unclear. This paper reviews the impact of gender differences in ASD, focusing on the female protective effect, DNA methylation, hormone levels, and clinical manifestations. It also discusses corresponding treatment options, particularly suggesting improvements in the diagnostic process, which is often overlooked, in order to provide valuable references for the clinical diagnosis and treatment of ASD.
Humans ; Autism Spectrum Disorder/genetics* ; Female ; Male ; DNA Methylation ; Sex Factors ; Sex Characteristics

The patient was a boy aged 1 year and 9 months who presented with 46,XY disorder of sex development (DSD), with severe undermasculinization of the external genitalia. Laboratory tests and ultrasound examinations showed normal functions of Leydig cells and Sertoli cells in the testes. Genetic testing revealed a novel pathogenic heterozygous variant, c.1186dupA (p.T396Nfs*17), in the PPP1R12A gene. Thirteen cases of PPP1R12A gene variants have been reported previously. These variants may cause isolated involvement of the genitourinary or neurological systems, or affect other systems/organs including the digestive tract, eyes, heart, etc. Patients with DSD typically present with a 46,XY karyotype and variable degrees of undermasculinization involving the external genitalia, gonads, and reproductive tract. This article reports a child with 46,XY DSD accompanied by growth retardation caused by a heterozygous variant in the PPP1R12A gene, which expands the clinical disease spectrum associated with PPP1R12A gene variants.
Humans ; Male ; Infant ; Disorder of Sex Development, 46,XY/etiology* ; Protein Phosphatase 1/genetics*