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 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 explore the genetic etiology of two patients with developmental delay and intellectual disability. METHODS: Two children who were respectively admitted to Henan Provincial People's Hospital on August 29, 2021 and August 5, 2019 were selected as the study subjects. Clinical data were collected, and array comparative genomic hybridization (aCGH) was carried out on the children and their parents for the detection of chromosomal microduplication/microdeletions. RESULTS: Patient 1 was a 2-year-and-10-month female and patient 2 was a 3-year-old female. Both children had featured developmental delay, intellectual disability, and abnormal findings on cranial MRI. aCGH revealed that patient 1 has harbored arr[hg19] 6q14.2q15(84621837_90815662)×1, a 6.19 Mb deletion at 6q14.2q15, which encompassed ZNF292, the pathogenic gene for Autosomal dominant intellectual developmental disorder 64. Patient 2 has harbored arr[hg19] 22q13.31q13.33(46294326_51178264)×1, a 4.88 Mb deletion at 22q13.31q13.33 encompassing the SHANK3 gene, haploinsufficiency of which can lead to Phelan-McDermid syndrome. Both deletions were classified as pathogenic CNVs based on the guidelines of American College of Medical Genetics and Genomics (ACMG) and were not found in their parents. CONCLUSION The 6q14.2q15 deletion and 22q13-31q13.33 deletion probably underlay the developmental delay and intellectual disability in the two children, respectively. Haploinsufficiency of the ZNF292 gene may account for the key clinical features of the 6q14.2q15 deletion.
Humans ; Child ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; Comparative Genomic Hybridization ; Chromosome Disorders/genetics* ; Chromosome Deletion ; Magnetic Resonance Imaging ; Chromosomes, Human, Pair 22 ; Developmental Disabilities/genetics* ; Carrier Proteins/genetics* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.
22q11 Deletion Syndrome/diagnostic imaging* ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis ; Ultrasonics

Phelan-McDermid syndrome (PMS)(OMIM#606232) is a rare genetic disorder caused by a deletion of the distal long arm of chromosome 22q13 involving a variety of clinical features with considerably heterogeneous degrees of severity. This syndrome is characterized by global developmental delay, intellectual disability, hypotonia, absent or severely delayed speech, minor dysmorphic features and autism spectrum disorder. PMS is easy to be misdiagnosed due to the lack of specific clinical manifestations. SHANK3 has been identified as the critical candidate gene for the neurological features of this syndrome. However, some studies have shown that other genes located in the 22q13 region may have a role in the formation of symptoms in individuals with PMS. This article provides a review for recent progress made in research on PMS including etiology, clinical manifestation, diagnosis, and treatment, with a particular emphasis on clinical diagnosis and treatment.
Autism Spectrum Disorder/genetics* ; Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 22 ; Humans ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To explore the genetic basis for an infant with multiple malformations including congenital heart disease and cleft palate. METHODS: The child and his parents were subjected to conventional chromosomal karyotyping and low-coverage massively parallel copy number variation sequencing (CNV-seq) analysis. RESULTS: The infant was found to have a 46,X,add(Y)(q11.23) karyotype, and his CNV-seq result was seq [hg19] 22q12.1q13.3 (29 520 001-51 180 000)× 3. His parents were found to be normal by both methods. CONCLUSION The additional chromosomal material found on Yq, verified as duplication of 22q12.1-q13.3, may account for the abnormal phenotype in this infant. CNV-seq has provided a useful complement for the diagnosis and more accurate information for genetic counseling.
Abnormalities, Multiple ; genetics ; Child ; Chromosome Duplication ; Chromosomes, Human, Pair 22 ; genetics ; Cleft Palate ; genetics ; DNA Copy Number Variations ; Genetic Testing ; Heart Defects, Congenital ; genetics ; Humans ; Infant ; Karyotyping

OBJECTIVE: To delineate the nature and origin of chromosomal aberration in a boy with mental retardation and multiple congenital deformities. METHODS: Chromosomal karyotypes of the proband and his parents were determined by routine G-banding analysis. Genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array). RESULTS: The karyotype of the proband was 46,X,add(Y)(q11.23). No karyotypic abnormality was detected in either parent. SNP array has identified a de novo 21.6 Mb duplication at 22q12qter in the proband. CONCLUSION The de novo 22q12qter duplication probably underlies the abnormalities in the proband.
Abnormalities, Multiple ; genetics ; Adult ; Child ; Chromosome Banding ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Genetic Testing ; Humans ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Trisomy

OBJECTIVE: To carry out genetic testing for 3 fetuses with abnormal prenatal screening. METHODS: Fetal ultrasound, karyotype analysis, single nucleotide polymorphism (SNP) array and fluorescence in situ hybridization were performed. RESULTS: Abnormalities of chromosome 22 were found with all 3 fetuses. Fetus 1 harbored a 7.1 Mb deletion in 22q13.2q13.33 region, which involved 54 OMIM genes including SHANK3 and FBLN1. Fetus 2 had a mosaicism karyotype, with 12% of cells harboring a 6.6 Mb deletion in 22q13.31q13.33, covering 48 OMIM genes such as SHANK3 and PPARA, and 5% of cells harboring a 26.1 Mb duplication in 22q11.1q13.2 involving 285 OMIM genes. Fetus 3 carried a tandem duplication of 1.7 Mb in 22q11.1q11.21, which involved 10 OMIM genes including CECR1, CECR2 and ATP6V1E1. No abnormality was found in the three couples by chromosomal karyotyping and SNP array analysis. CONCLUSION The severity of diseases caused by chromosome 22 abnormalities not only depends on the range of the deletion or duplication, but is also closely related to chromosome structure, gene dose and genetic environment. Combined ultrasonography and various genetic testing techniques in prenatal diagnosis can greatly increase the detection rate of genetic diseases with substantial phenotypic variation.
Chromosome Aberrations ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Fetus ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Transcription Factors ; Ultrasonography, Prenatal

OBJECTIVE: To carry out prenatal diagnose for a fetus with ultrasonography abnormalities using multiple genetic techniques. METHODS: Routine G-banding chromosomal analysis and single nucleotide polymorphism array (SNP-array) were applied in conjunction for the prenatal diagnosis of the fetus. The result was confirmed by fluorescence in situ hybridization (FISH). RESULTS: SNP-array detected that the fetus has carried a hemizygous 5.1 Mb deletion at 22q13.31q13.33, which is associated with Phelan-McDermid syndrome, and a hemizygous 4.5 Mb deletion at 21q21.1q21.2. FISH analysis of the fetus and its parents suggested that both deletions were de novo in origin. CONCLUSION The hemizygous deletions on 21q21.1q21.2 and 22q13.31q13.33 probably underlay the abnormal phenotype of the fetus. Genetic analysis can provide crucial information for the prenatal diagnosis and genetic counseling.
Chromosome Deletion ; Chromosome Disorders/genetics* ; Chromosomes, Human, Pair 21/genetics* ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion/genetics*