OBJECTIVE: To explore the clinical and genetic characteristics of two children with Williams-Beuren syndrome (WBS). METHODS: Two children who had presented at the Department of Pediatrics, General Hospital of Ningxia Medical University respectively on January 26 and March 18, 2021 were selected as the study subjects. Clinical data and results of genetic testing of the two patients were analyzed. RESULTS: Both children had featured developmental delay, characteristic facies and cardiovascular malformation. Child 1 also had subclinical hypothyroidism, whilst child 2 had occurrence of epilepsy. Genetic testing revealed that child 1 has harbored a 1.54 Mb deletion in the 7q11.23 region, whilst child 2 has a 1.53 Mb deletion in the same region, in addition with a c.158G>A variant of the ATP1A1 gene and a c.12181A>G variant of the KMT2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.158G>A and c.12181A>G variants were rated as variants of unknown significance (PM1+PM2_Supporting+PP2+PP3；PM2_Supporting). CONCLUSION Both children had characteristic features of WBS, for which deletions of the 7q11.23 region may be accountable. For children manifesting developmental delay, facial dysmorphism and cardiovascular malformations, the diagnosis of WBS should be suspected, and genetic testing should be recommended to confirm the diagnosis.
Child ; Humans ; Williams Syndrome/diagnosis* ; Genetic Testing ; Facies ; Epilepsy/genetics* ; Chromosomes, Human, Pair 7/genetics* ; Chromosome Deletion

OBJECTIVE: To explore the genetic basis for a child with supravalvular aortic stenosis. METHODS: The child and his parents were subjected to conventional G-banding karyotyping, array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. RESULTS: No karyotypic abnormality was detected in the child and his parents. aCGH has identified a de novo 278 kb deletion encompassing the ELN gene in 7q11.23, which overlapped with the critical region of Williams-Beuren syndrome (WBS). MLPA has confirmed above findings. CONCLUSION The proband was diagnosed with atypical WBS. Deletion of the ELN gene may predispose to supravalvular aortic stenosis in the proband.
Aortic Stenosis, Supravalvular ; genetics ; Child ; Chromosome Banding ; Chromosomes, Human, Pair 7 ; genetics ; Comparative Genomic Hybridization ; Gene Deletion ; Genetic Testing ; Humans ; Williams Syndrome ; complications ; genetics

OBJECTIVE: To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology. METHODS: Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs. RESULTS: Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal. CONCLUSION The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.
Chromosome Deletion ; Chromosomes, Human, Pair 7 ; genetics ; Cytoplasmic Dyneins ; genetics ; DNA Copy Number Variations ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Limb Deformities, Congenital ; genetics

OBJECTIVE: To correlate genotype with clinical phenotype of a child featuring multiple congenital malformations. METHODS: Clinical examination of the patient was carried out. Chromosome microarray analysis (CMA) was employed to detect genomic copy number variations (CNVs), and quantitative PCR (qPCR) was used for verifying the result. RESULTS: The child had congenital heart disease (ventricular septal defect, atrial septal defect, pulmonary arterial hypertension, and tricuspid regurgitation), psychomotor retardation, agenesis of corpus callosum, hypospadias and scoliosis. CMA has detected a 1.8 Mb deletion at 7p22.3, a 1.8 Mb duplication at 7p22.3p22.2 and a 23.5 Mb duplication at 7q33q36.3 in the fetus, all of which were de novo in origin. CONCLUSION CMA can precisely detect microdeletion/duplications and facilitate the genotype-phenotype correlation analysis.
Abnormalities, Multiple ; genetics ; Child ; Chromosomes, Human, Pair 7 ; genetics ; DNA Copy Number Variations ; Genetic Testing ; Heart Defects, Congenital ; genetics ; Humans ; Male ; Phenotype ; Sequence Deletion

OBJECTIVE: To carry out genetic diagnosis for a pregnant woman and her fetus. METHODS: Chromosome G-banding and microarray analysis were used to analyze the woman featuring dysmorphism and recognition defect and her fetus featuring developmental retardation. RESULTS: The karyotype of the woman was normal, but chromosome microarray analysis showed that she has carried a 1423 kb deletion at 7q11.23 region. Her fetus has carried a 1530 kb deletion at the same region. Both individuals were diagnosed as Williams-Beuren syndrome. CONCLUSION Familiarity with its clinical features and proper selection of genetic testing methods are crucial for the diagnosis of Williams-Beuren syndrome.
Child ; Chromosome Banding ; Chromosomes, Human, Pair 7 ; Female ; Genetic Testing ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Williams Syndrome ; diagnosis

Williams syndrome is a rare congenital disorder with various physical abnormalities and characterized by facial, oral, and dental features. Individuals with Williams syndrome typically have eating disorders in the early childhood, which lead to prolonged night feeding. Prolonged night feeding is a risk factor for rampant dental caries. Williams syndrome is caused by the microdeletion of chromosome 7, resulting in elastin deficiency. Elastin is integral to cardiovascular health. Many patients with Williams syndrome have complex cardiovascular abnormalities that must be considered a part of dental management. Complications related to cardiovascular diseases may induce adverse effects such as dangerously elevated blood pressure. This may occur in patients during stressful dental treatment. In addition, characteristics of auditory hyperalgesia and anxiety disorders among patients with William syndrome, complicate receiving routine dental management. Therefore, dental treatment under sedation or general anesthesia may be preferable for patients with Williams syndrome; in particular, patients who are very uncooperative and/or needs extensive dental treatment. A thorough evaluation of each patient's physical condition is required before making decisions regarding dental treatment. Careful monitoring and preparation for emergencies are very important during and shortly after dental treatment under general anesthesia or sedation. Monitoring is critical until vital signs have stabilized and return to normal. A 28-month-old man diagnosed as having Williams syndrome, visited the Dental Hospital of OO University for the management of rampant dental caries. We reported on the management of this patient who had peripheral pulmonic stenosis, and received dental treatment under general anesthesia. We also reviewed the characteristics of Williams syndrome and discussed considerations for dental treatment under general anesthesia.
Anesthesia, General ; Anxiety Disorders ; Blood Pressure ; Cardiovascular Abnormalities ; Cardiovascular Diseases ; Child, Preschool ; Chromosomes, Human, Pair 7 ; Congenital, Hereditary, and Neonatal Diseases and Abnormalities ; Dental Caries ; Eating ; Elastin ; Emergencies ; Humans ; Hyperalgesia ; Pulmonary Valve Stenosis ; Risk Factors ; Vital Signs ; Williams Syndrome

OBJECTIVETo explore the application of combined techniques for the prenatal diagnosis of a case with 7q11.23 duplication.

METHODSAmniocentesis was performed in the second trimester for a mother with a high risk suggested by serological prenatal screening. G-banded chromosomal analysis was performed on cultured amniocytes and peripheral blood samples from both parents. DNA from amniotic fluid sample was isolated for a BACs-on-Beads (BoBs) assay. To define the range of duplication, copy number variation was determined with single nucleotide polymorphism array (SNP array, Affymetrix CytoScan 750K) and fluorescence in situ hybridization (FISH) analysis.

RESULTSChromosomal analysis suggested that the fetus and both parents all had a normal karyotype, while a duplication of 7q11.23 was detected by the BoBs assay. SNP array revealed a 1.5 Mb duplication in chromosome 7q11.23, which was confirmed by FISH.

CONCLUSIONCombined prenatal BoBs, SNP array and FISH has enabled effective diagnose of a case with 7q11.23 syndrome.

Adult ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; Trisomy ; genetics

Patients with a duplication from 7q36 to the terminus or a deletion of 9p24 have been reported, whereas those harboring both mutations have not. Here, we report a patient with simultaneous de novo 7q36.1-q36.3 duplication and 9p24.3 deletion. A 6-year-old boy presented with speech developmental delay, microcephaly, and dysmorphic features, including a long face and small nose. Chromosome and array comparative genomic hybridization analyses revealed 46,XY,dup(7)(q36.1-q36.3) and del(9)(p24.3). The sizes of the duplication and deletion were 9.9 Mb and 1.9 Mb, respectively. The duplication of chromosome 7 contained 68 known genes, of which 3 are related with entries in the Developmental Disorders Genotype-to-Phenotype (DDG2P) database. The deletion of chromosome 9 contained 6 known genes, of which 2 are in the DDG2P database. We investigated the genotype and phenotype in this patient, and reviewed the relevant literatures for possible clinical presentation in these variations.
Child ; Chromosome Disorders ; Chromosomes, Human, Pair 7 ; Chromosomes, Human, Pair 9 ; Comparative Genomic Hybridization ; Developmental Disabilities ; Genotype ; Humans ; Male ; Microcephaly ; Nose ; Phenotype

OBJECTIVETo investigate the clinical application of fluorescent in situ hybridization (FISH) for the differential diagnosis of myelodysplastic syndromes (MDS) and aplastic anemia (AA).

METHODSA FISH kit capable of detecting the chromosomal abnormalities related to MDS was used to analyze 94 patients who were suspected to have AA by bone marrow morphology.

RESULTSCytogenetic abnormalities were detected in 11 of the 94 patients, which included trisomy 8 (5 cases), 20q- (1 case) and -Y (1 case). There were 4 cases related to MDS, which included 3 cases of 5q-, in which 1 case carry 20q- at the same time, and 7q- (1 case). No significant difference was found between the MDS and AA groups in terms of age, sex or routine blood examination including absolute neutrophil count, hemoglobin content and platelet count.

CONCLUSIONFISH can detect certain cytogenetic abnormalities related to MDS in patients morphologically diagnosed as AA.

Adolescent ; Adult ; Aged ; Anemia, Aplastic ; diagnosis ; genetics ; Bone Marrow Cells ; cytology ; Child ; Chromosome Aberrations ; Chromosomes, Human, Pair 7 ; genetics ; Chromosomes, Human, Pair 8 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Male ; Middle Aged ; Trisomy ; genetics

OBJECTIVETo apply single nucleotide polymorphism array (SNP-array) for the diagnosis of Williams-Beuren syndrome (WBS) in a patient.

METHODSChromosome G-banding and SNP-array were used to analyze a girl featuring mental retardation.

RESULTSThe karyotypes of the child and her parents were all normal, but SNP-array showed a 1.9 Mb deletion at 7q11.23 in the patient. The same deletion was not found in her parents.

CONCLUSIONThe mental retardation and special facies of the girl were probably due to the 7q11.23 microdeletion. SNP-array has an important value for the diagnosis of mental retardation.

Child ; Chromosome Deletion ; Chromosomes, Human, Pair 7 ; Female ; Humans ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Williams Syndrome ; genetics