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

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

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

Adult ; Aged ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Humans ; Male ; Middle Aged ; Pedigree ; Polydactyly ; genetics

OBJECTIVETo perform genetic analysis for two patients with supravalvular aortic stenosis and unusual facial features.

METHODSCytogenetic and molecular genetic methods including chromosome karyotyping, multiplex ligation-dependent probe amplification (MLPA) and single nucleotide polymorphism array (SNP-array) were performed to detect potential mutation in the patients.

RESULTSNo abnormal karyotype was detected in either patient. Deletions in 7q11.23 region (1.36 Mb and 1.73 Mb, respectively) were discovered by SNP-array for the two patients. In both patients, de novo heterozygous deletion of ELN and LIMK1 genes was confirmed by MLPA analysis.

CONCLUSIONThe genotypes of the two patients were identified by molecular genetic analysis, which has facilitated interpretation of the phenotypes of these patient. According to the deletion mutation, prenatal diagnosis for the family could be performed in the future.

Child ; Chromosome Deletion ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Genotype ; Humans ; Infant ; Lim Kinases ; genetics ; Male ; Phenotype ; Williams Syndrome ; genetics

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 explore the genetic cause for a child with mental retardation, developmental delay and multi-systemic developmental disorders by analyzing the copy number variations (CNVs) and correlating the genotype with the phenotype.

METHODSRoutine G-banding was performed to analyze the karyotype of the patient and her parents. In addition, single nucleotide polymorphisms array (SNP-array) was used to determine the CNVs, which was confirmed by fluorescence in situ hybridization (FISH).

RESULTSNo karyotypic abnormality was detected upon chromosome analysis. However, SNP-array has identified a de novo hemizygous deletion of 1673 kb on chromosome region 7q11.23, which has been associated with Williams-Beuren syndrome. The microdeletion was confirmed by FISH testing.

CONCLUSIONA child with Williams-Beuren syndrome has been diagnosed by SNP-array and FISH. The de novo 7q11.23 microdeletion probably underlies the clinical manifestation of the patient. Compared with routine karyotype analysis, SNP-array is more useful for diagnosing children with multiple congenital anomalies with unclear etiology.

Adult ; Asian Continental Ancestry Group ; genetics ; Child, Preschool ; China ; Chromosome Banding ; Chromosomes, Human, Pair 7 ; genetics ; DNA Copy Number Variations ; Female ; Humans ; Karyotyping ; Male ; Pedigree ; Polymorphism, Single Nucleotide ; Williams Syndrome ; diagnosis ; genetics