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

This article reports a child with cardioaciocutaneous syndrome (CFCS) caused by a rare microdeletion of chromosome 19p13.3, and a literature review is conducted. The child had unusual facies, short stature, delayed mental and motor development, macrocephaly, and cardiac abnormalities. Whole-exome sequencing identified a 1 040 kb heterozygous deletion in the 19p13.3 region of the child, which was rated as a "pathogenic variant". This is the first case of CFCS caused by a loss-of-function mutation reported in China, which enriches the genotype characteristics of CFCS. It is imperative to enhance the understanding of CFCS in children. Early identification based on its clinical manifestations should be pursued, and genetic testing should be performed to facilitate diagnosis.
Humans ; Chromosome Deletion ; Chromosomes, Human, Pair 19/genetics* ; Ectodermal Dysplasia/genetics* ; Facies ; Failure to Thrive/genetics* ; Heart Defects, Congenital/genetics*

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

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 clinical phenotype and genetic characteristics of four patients with Phelan-McDermid syndrome (PMS) due to variants of SHANK3 gene. METHODS: Four patients diagnosed with PMS at Guangzhou Women and Children's Medical Center Liuzhou Hospital from January 2020 to January 2025 were selected as the study subjects. Clinical data of the patients were collected. Peripheral venous blood samples were collected from each patient for the extraction of genomic DNA, followed by whole-exome sequencing (WES) and validation by Sanger sequencing. Pathogenicity of candidate variants was rated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), and multiple bioinformatic tools were used to assess the pathogenic effects of the variants. The study was approved by the Ethics Committee of the Hospital (Ethics No. 2025-007). RESULTS: All four patients had exhibited language delay and intellectual disability (IQ 35 ~ 65). Some also presented with autism spectrum disorder and schizophrenia, albeit with significant phenotypic heterogeneity. All patients were found to harbor deletions of 22q13.33 region, ranging from 55.46 Kb to 112.64 Kb, primarily involving the SHANK3 gene. CONCLUSION PMS is typically caused by deletions or mutations of the SHANK3 gene. The clinical manifestations are diverse, with developmental delay and intellectual disability being the most common. Accurate diagnosis requires integration of genetic testing and standardized clinical assessment. Genetic screening for suspected patients and at-risk pregnant women is recommended to facilitate their genetic counseling.
Child ; Humans ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Exome Sequencing ; Nerve Tissue Proteins/genetics* ; Phenotype

OBJECTIVE: To analyze the clinical and genetic features of a child with Primary ciliary dyskinesia (PCD) due to compound heterozygous variants of the CCDC39 gene and a 22q11.21 deletion, and to explore the potential role of the two types of variants in the formation of complex phenotypes. METHODS: A child presented at the Shanxi Children's Hospital in March 2025 due to multiple congenital anomalies was selected as the study subject. Peripheral blood samples were taken from the child and her parents and subjected to whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Effect of splicing variant was predicted using SpliceAI, and pathogenicity was assessed based on the ACMG guidelines. Copy number variation (CNV) analysis was also performed. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No.: IRB-WZ-2025-019). RESULTS: The patient has exhibited multiple features including severe pneumonia, bronchiectasis, localized pulmonary emphysema, scoliosis, tetralogy of Fallot, and atrial septal defect. Genetic testing revealed that she has harbored compound heterozygous variants of the CCDC39 gene, namely c.1167+1G>A and c.1009A>T, which were inherited from her father and mother, respectively, with the latter being a novel likely pathogenic variant. In addition, a heterozygous deletion of approximately 708 kb at 22q11.21 was detected. CONCLUSION The coexistence of CCDC39 gene variants and a 22q11.21 deletion may underlay the development of complex clinical phenotypes in this child.
Humans ; Female ; Chromosomes, Human, Pair 22/genetics* ; Chromosome Deletion ; DNA Copy Number Variations/genetics* ; Child ; Ciliary Motility Disorders/genetics* ; Exome Sequencing

OBJECTIVE: To investigate the clinical characteristics and genetic etiology in a fetus with 12q14 microdeletion syndrome. METHODS: A fetus diagnosed with 12q14 microdeletion syndrome at Wenzhou People's Hospital in July 2019 was selected as the study subject. The fetus was from a twin pregnancy by in vitro fertilization-embryo transfer, with ultrasound findings including growth restriction, cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Clinical data and family history were collected. Amniotic fluid sample was collected from both twins, and peripheral blood samples were obtained from their parents. Amniocytic karyotyping analysis and chromosomal microarray analysis (CMA) were performed, and familial validation was conducted. This study was approved by the Medical Ethics Committee of Wenzhou People's Hospital (Ethics No.: KY-202408-034). RESULTS: Prenatal ultrasound showed no significant abnormality in one of the twins, whilst the other twin exhibited severe growth restriction accompanied by cleft lip/palate, ventricular septal defect, tricuspid regurgitation, and pericardial effusion. Karyotyping and CMA analyses of first twin showed no abnormalities, whilst the second twin had a chromosomal karyotype of 46,XN,t(3;12)(q26.3;q14), and CMA revealed a 4.9 Mb deletion in the 12q14.3-q15 region (arr[hg19]12q14.3q15(65,574,059_70,488,106)x1). Karyotyping and CMA analyses of both parents revealed no abnormalities, confirming that the fetus deletion was de novo in origin. Literature review suggested that prenatal diagnosis of 12q14 microdeletion syndrome has been extremely rare. CONCLUSION The fetus was diagnosed with 12q14 microdeletion syndrome. This de novo deletion may have dervied from chromosomal translocation. As a first-tier prenatal diagnostic technique, CMA can effectively detect microdeletion/microduplications missed by conventional karyotyping analysis.
Humans ; Female ; Pregnancy ; Chromosome Deletion ; Chromosomes, Human, Pair 12/genetics* ; Karyotyping ; Adult ; Prenatal Diagnosis ; Chromosome Disorders/diagnosis* ; Ultrasonography, Prenatal ; Fetus ; Male

Humans ; Chromosome Deletion ; Chromosome Duplication

After the promulgation of the first edition of expert consensus on the application of chromosomal microarray analysis (CMA) technology in prenatal diagnosis in 2014, after 8 years of clinical and technical development, CMA technology has become a first-line diagnosis technology for fetal chromosome copy number deletion or duplication abnormalities, and is widely used in the field of prenatal diagnosis in China. However, with the development of the industry and the accumulation of experience in case diagnosis, the application of CMA technology in many important aspects of prenatal diagnosis, such as clinical diagnosis testimony, data analysis and genetic counseling before and after testing, needs to be further standardized and improved, so as to make the application of CMA technology more in line with clinical needs. The revision of the guideline was led by the National Prenatal Diagnostic Technical Expert Group, and several prenatal diagnostic institutions such as Peking Union Medical College Hospital were commissioned to write, discuss and revise the first draft, which was discussed and reviewed by all the experts of the National Prenatal Diagnostic Technical Expert Group, and was finally formed after extensive review and revision. This guideline is aimed at the important aspects of the application of CMA technology in prenatal diagnosis and clinical diagnosis, from the clinical application of evidence, test quality control, data analysis and interpretation, diagnosis report writing, genetic counseling before and after testing and other work specifications are elaborated and introduced in detail. It fully reflects the integrated experience, professional thinking and guidance of the current Chinese expert team on the prenatal diagnosis application of CMA technology. The compilation of the guideline for the application of CMA technology in prenatal diagnosis will strive to promote the standardization and advancement of prenatal diagnosis of fetal chromosome diseases in China.
Female ; Humans ; Pregnancy ; Asian People ; Chromosome Aberrations ; Chromosome Deletion ; Chromosome Duplication/genetics* ; DNA Copy Number Variations/genetics* ; Fetal Diseases/genetics* ; Genetic Counseling ; Microarray Analysis ; Prenatal Care ; Prenatal Diagnosis ; Practice Guidelines as Topic

Humans ; Amino Acid Metabolism, Inborn Errors/genetics* ; Haploinsufficiency