Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*

OBJECTIVE: To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling. METHODS: One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children's Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher's exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children's Hospital (Ethics No.: QFELL-YJ-2025-85). RESULTS: Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. CONCLUSION CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; DNA Copy Number Variations/genetics* ; Kidney/abnormalities* ; Adult ; Ultrasonography, Prenatal ; Urogenital Abnormalities/diagnosis* ; Microarray Analysis/methods* ; Retrospective Studies ; Urinary Tract/abnormalities* ; Fetus ; Pregnancy Outcome ; Vesico-Ureteral Reflux

Female ; Humans ; Consensus ; East Asian People ; Urogenital Abnormalities/surgery* ; Sexual Dysfunction, Physiological/surgery*

OBJECTIVE: To analyze the clinical phenotype and genetic basis for a male neonate featuring hypoparathyroidism, sensorineural hearing loss, and renal dysplasia (HDR) syndrome. METHODS: The child was subjected to genome-wide copy number variation (CNVs) analysis and whole exome sequencing (WES). Clinical data of the patient was analyzed. A literature review was also carried out. RESULTS: The patient, a male neonate, had presented with peculiar facial appearance, simian crease and sacrococcygeal mass. Blood test revealed hypocalcemia, hypoparathyroidism. Hearing test suggested bilateral sensorineural deafness. Doppler ultrasound showed absence of right kidney. Copy number variation sequencing revealed a 12.71 Mb deletion at 10p15.3-p13 (chr10: 105 001_12 815 001) region. WES confirmed haploinsufficiency of the GATA3 gene. With supplement of calcium and vitamin D, the condition of the child has improved. CONCLUSION The deletion of 10p15.3p13 probably underlay the HDR syndrome in this patient.
DNA Copy Number Variations ; Hearing Loss, Sensorineural/genetics* ; Humans ; Hypoparathyroidism/genetics* ; Infant, Newborn ; Kidney/abnormalities* ; Male ; Syndrome ; Urogenital Abnormalities/genetics*

OBJECTIVE: To analyze the clinical manifestations and gene variants of patients with blepharophimosis, ptosis and epicanthus inversus syndrome (BPES). METHODS: Clinical data of 7 pedigrees affected with BPES were collected, and genomic DNA was extracted from peripheral blood samples of the probands and their relatives. All exons of the FOXL2 gene were subjected to Sanger sequencing. Those with negative findings were further screened by targeted capture and next generation sequencing (NGS) and microarray analysis. Pathogenicity of candidate variants were predicted by search of PubMed and related databases, and the impact of the variants was interpreted by protein prediction software. Diagnosis was confirmed by clinical phenotype, medical history and mutation analysis. RESULTS: A pathogenic variant was identified in six of the 7 pedigrees, which included four known pathogenic variants and one novel FOXL2 c.299dupA variant. A heterozygous 3q22.3q23 deletion, which encompassed the FOXL2 gene, was identified in another pedigree.As predicted, the c.299dupA frameshift mutation of FOXL2 gene can lead to the premature termination of protein translation, which is pathogenic. CONCLUSION A novel and 5 known pathogenic variants have been identified in six pedigrees affected with BPES by the combined Sanger sequencing, target capture NGS and microarray analysis. Above findings have enabled genetic counseling and prenatal diagnosis for these pedigrees.
Blepharophimosis/genetics* ; Forkhead Box Protein L2/genetics* ; Forkhead Transcription Factors/genetics* ; Humans ; Mutation ; Pedigree ; Phenotype ; Skin Abnormalities ; Urogenital Abnormalities

Muüllerian duct anomalies (MDAs) are congenital defects arising from probable teratogenic assault at 6–22 weeks of gestation.Uterine didelphys arises from complete lack of fusion of Muüllerian ducts, resulting in two entirely separate hemiuteri, cervices and vaginas.The incidence of MDA is <5% and the frequency of uterine didelphys is 1 in 1000–30,000 women and twin pregnancy in uterus didelphys is only 1 in a million. This is a case of a gravida 1 para 0, with uterine didelphys and unilateral renal agenesis diagnosed of single live intrauterine pregnancy in the left half of uterine didelphys who had a spontaneous passage of meaty material from the right hemiuterus which were histopathologically consistent with degenerating products of conception, hence confirming a dicavitary twin pregnancy. Management should be wholistic encompassing preconception, prenatal, intrapartum, and postpartum period as any complications may arise at any point.
Uterine Anomalies ; Urogenital Abnormalities ; Abortion, Spontaneous

Cloacal malformations are characterized by the confluence of the lower urinary tract, the female reproductive tract, and the rectum to create a common channel with a single opening on the perineum. The presence of a cloaca is a normal phase of early human embryological development. Between the 4^th and 7^th weeks of gestation, the cloaca undergoes subdivision to form the hindgut and urogenital sinus. Failure of this process results in the congenital anomaly termed persistent cloaca (PC). The term urorectal septum malformation sequence (URSMS) is also used to describe this anomaly. The classic description of this process which is still cited in many standard textbooks dates from the 19^th century. However, this has been increasingly called into question by the findings of studies using modern scientific methodology. Urogenital sinus anomalies are defined by the confluence of the urethra and vagina to form a common channel of varying length with a single perineal opening. In this condition, the anorectal canal opens separately on the perineum. The presence of a urogenital sinus represents a transient phase of the normal development of the lower genital tract in the female fetus. However, the form of urogenital sinus most commonly encountered in the developed world is a feature of disordered sexual differentiation and does not arise simply from the persistence of the anatomical structure which is a feature of normal fetal development.
Cloaca/embryology* ; Female ; Humans ; Urogenital Abnormalities/embryology* ; Vagina/embryology*

Herlyn-Werner-Wunderlich syndrome, characterized by uterus didelphys with blind hemivagina and ipsilateral renal agenesis, is a rare Mullerian duct anomaly. This case series shows a wide spectrum of the condition, one presenting in an adolescent, managed conservatively and the other in the perimenopausal age group given a more definitive management. The first case is an 18-year- old nulligravid who manifested with progressive dysmenorrhea and foul smelling vaginal discharge a few years after menarche. She subsequently underwent vaginal septotomy followed by diagnostic hysteroscopy. On the other hand, the second case is a 46- year-old nulligravid whose chief complaint is a foul smelling vaginal discharge and consequently went through a total abdominal hysterectomy with salpingo-oophorectomy. To our knowledge, the second case is the only patient diagnosed in the perimenopausal stage and underwent a total hysterectomy. Ultrasound is the first-line imaging modality used in both cases and its merits are highlighted to prove its importance and diagnostic value in the workup of this condition.
Mullerian aplasia ; Mullerian Ducts ; Urogenital Abnormalities

Adult ; Azoospermia/pathology* ; Carbonic Anhydrases/genetics* ; Congenital Abnormalities/genetics* ; Epithelial Sodium Channels/genetics* ; Gene Expression Regulation/genetics* ; Genome, Human ; Humans ; Infertility, Male/genetics* ; Male ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities*

WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome is a rare contiguous gene deletion syndrome caused by deleting genes including WT1 and PAX6 genes in 11p13 region, which is characterized by Wilms tumor, aniridia, genitourinary abnormalities, and intellectual disability. We report the clinical and cytogenetic characteristics of one Korean patient with WAGR syndrome. The patient shows bilateral sporadic aniridia and genital anomalies at 2 months of age. A heterozygous 14.5 Mb interstitial deletion of 11p14.3p12 region was detected by array comparative genomic hybridization. At 2 years and 10 months of age, Wilms tumor is found through regularly abdominal ultrasonography and treated by chemotherapy, radiation therapy and surgery.
Aniridia ; Comparative Genomic Hybridization ; Cytogenetics ; Drug Therapy ; Gene Deletion ; Humans ; Intellectual Disability ; Ultrasonography ; Urogenital Abnormalities ; WAGR Syndrome* ; Wilms Tumor*