OBJECTIVE: To explore the coincidence rate of G-banding karyotype analysis and fluorescence in situ hybridization (FISH) for the diagnosis of children with sex chromosome mosaicisms. METHODS: A retrospective analysis was carried out for 157 children with suspected sex chromosome abnormalities who had presented at Shenzhen Children's Hospital from April 2021 to May 2022. Interphase sex chromosome FISH and G-banding karyotyping results were collected. The coincidence rate of the two methods in children with sex chromosome mosaicisms was compared. RESULTS: The detection rates of G-banding karyotype analysis and FISH were 26.1% (41/157) and 22.9% (36/157) , respectively (P > 0.05). The results of G-banding karyotype analysis showed that 141 cases (89.8%) were in the sex chromosome homogeneity group, of which only 5 cases (3.5%) were inconsistent with the results of FISH. There were 16 cases (10.2%) in the sex chromosome mosaicism group, of which 11 cases (68.8%) were inconsistent with the results of FISH. There was a statistical difference between the two groups in the coincidence rate of the results of the two methods (P < 0.05). CONCLUSION No significant difference was found between G-banding karyotype analysis and FISH in the detection rate of chromosome abnormalities. The coincidence rate in the mosaicism group was lower than that in the homogeneity group, and the difference was statistically significant. The two methods should be combined for clinical diagnosis.
Humans ; Mosaicism ; In Situ Hybridization, Fluorescence/methods* ; Retrospective Studies ; Karyotyping ; Chromosome Aberrations ; Sex Chromosome Aberrations ; Karyotype ; Chromosome Banding ; Sex Chromosomes

OBJECTIVETo explore the clinical and genetic characteristics of a case with Pallister-Killian syndrome (PKS).

METHODSChromosomal karyotype of umbilical cord blood sample derived from a 36-year-old pregnant woman was analyzed by G-banding analysis. After birth, the child was further analyzed with single nucleotide polymorphism microarray (SNP array) and fluorescence in situ hybridization (FISH) using 12pter/12qter probes.

RESULTSG-banding analysis showed that the fetus has a karyotype of 46,XY [77]/47,XY,+mar [23]. After birth, Affymetrix CytoScan 750K array analysis showed a segmental tetrasomy of arr [hg19] 12p13.33p11.1(173 786 - 34 835 641)×4 and a 34.6 Mb repeat at 12p13.33p11.1 with in the neonate. FISH analysis confirmed that 39% of cells harbored the 12p tetrasomy.

CONCLUSIONCombined clinical examination, G-banded chromosomal karyotyping, FISH and microarray analysis can delineate the origin and fragments of small supernumerary marker chromosomes and diagnose PKS with precision.

Adult ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; Chromosomes, Human, Pair 12 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Karyotyping ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVETo analyze three cases with partial 21q trisomy, and correlate their genotypes with phenotypes.

METHODSG-banding chromosomal analysis and single nucleotide polymorphism (SNP array) were performed for the three cases and their parents.

RESULTSSNP array has detected partial 21q trisomy in three cases and one mother, with variable size and location of the duplications. Case 1 harbored a 12.35 Mb duplication at 21q22.11q22.3, which spanned the Down syndrome critical region. Case 2 harbored a 35.32 Mb duplication at 9p24.3p13.3 and a 14.42 Mb duplication at 21q11.2q21.3, with the former spanning the partial 9p trisomy syndrome critical region excluding the Down syndrome critical region, and was inherited from his mother. Case 3 harbored a 4.17 Mb tetraploidy at 21q11.2q21.1 in the form of mosaicism, which spared the Down syndrome critical region. His mother carried a 4.17 Mb triploidy at 21q11.2q21.1, which was also a mosaicism.

CONCLUSIONPartial 21q trisomy may occur in various forms and its clinical phenotypes are heterogeneous. Combined use of genetic techniques, particularly SNP array, is crucial for diagnosing partial 21q trisomy and delineating its genotype-phenotype correlation.

Child, Preschool ; Chromosome Banding ; Down Syndrome ; genetics ; Female ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; Microarray Analysis ; methods ; Polymorphism, Single Nucleotide

OBJECTIVETo carry out chromosomal microarray analysis (CMA) on four fetuses with abnormal karyotypes.

METHODSAmniotic fluid samples were obtained and subjected to routine G-banded karyotyping analysis. CMA was applied for cultured amniocytes to determine alterations of gene dosage and chromosomal breakpoints.

RESULTSAbnormal karyotypes were found in the parents of 3 fetuses. Parental karyotypes of the remaining fetus were normal. Imbalance chromosome rearrangements were revealed by CMA in all 4 cases.

CONCLUSIONCMA is an effective tool for the evaluation of clinical significance and delineation of the breakpoints involved in complex chromosomal rearrangements.

Abnormal Karyotype ; Adult ; Chromosome Banding ; Female ; Humans ; Karyotyping ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo perform molecular cytogenetic study on two fetuses with abnormal ultrasound findings and analyze their genotype-phenotype correlation.

METHODSG-banded karyotyping, single nucleotide polymorphism array (SNP array) and fluorescence in situ hybridization (FISH) were performed on amniotic fluid cells from both fetuses and peripheral blood samples from their parents. Results of SNP array were analyzed with bioinformatics software.

RESULTSG-banded karyotyping failed to detect any abnormalities in both fetuses and their parents. SNP array detected a 2.484 Mb terminal deletion at 17p13.3 [arr[hg19] 17p13.3 (83 035-2 567 405)×1] in fetus 1 and a 3.295 Mb terminal deletion at 17p13.3p13.2 [arr[hg19] 17p13.3p13.2 (83 035- 3 377 560)×1] in fetus 2. Both deletions have overlapped with the critical region of Miller-Dieker syndrome (MDS) and involved candidate genes such as PAFAH1B1, YWHAE and CRK. In addition, SNP array and FISH analyses on the parental peripheral blood samples demonstrated that both 17p13.3 and 17p13.3p13.2 deletions were of de novo origin. Metaphase FISH performed on amniotic fluid cells confirmed the presence of 17p13.3 and 17p13.3p13.2 deletions detected by the SNP array, while metaphase FISH performed on the parents excluded any potential chromosome rearrangements.

CONCLUSIONAbnormal ultrasound features for fetuses with MDS mainly include central nervous system anomalies. SNP array can efficiently detect 17p13.3 microdeletions underlying MDS, and accurately map the breakpoints and involved genes, which may facilitate understanding of the genotype and phenotype correlations for MDS.

Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; genetics ; Classical Lissencephalies and Subcortical Band Heterotopias ; diagnostic imaging ; genetics ; Female ; Fetal Diseases ; diagnostic imaging ; genetics ; Genetic Association Studies ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Phenotype ; Polymorphism, Single Nucleotide ; Pregnancy ; Ultrasonography, Prenatal ; methods

OBJECTIVETo investigate the genetic cause and prognosis of a fetus with a rare karyotype.

METHODSFluorescence in situ hybridization (FISH) was used for verifying a structural chromosomal abnormality detected by conventional karyotyping analysis. Whole genome DNA microarray was used to analyze copy number variations carried by the fetus.

RESULTSThe fetus was found to have a 46,XX,dup(21)(?q21q22) karyotype, which was verified by FISH analysis as repetition of chromosome 21 region, namely nuc ish 21q22×3. Whole genome DNA microarray confirmed that there was a 17.87 Mb duplication in the 21q21.3q22.3 region, which involved GATA1, JAK2 and ALL genes and spanned the Down syndrome region. The genes are implicated in craniofacial abnormalities, cardiac abnormalities, mental retardation, growth retardation, limb abnormalities. In addition, there was also an 8.43 Mb deletion in the 4p16.1p16.3 region, which involved FGFR3, LETM1, WHSC1 and WHSC2 and other 64 OMIM genes and spanned the Wolf-Hirschhorn syndrome region. The genes are implicated in growth retardation, craniofacial abnormalities, cardiac abnormalities, mental retardation, and hypotonia. After consultation, the family chose to terminate the pregnancy at 25th week of gestation.

CONCLUSIONFISH can help to verify structural chromosome abnormalities suspected by conventional karyotyping analysis. Combined with whole genome microarray, these can determine copy number variation and its region containing the disease genes, and facilitate clinical analysis of the fetus.

Abortion, Eugenic ; Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; genetics ; Chromosome Duplication ; Chromosomes, Human, Pair 21 ; genetics ; Chromosomes, Human, Pair 4 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Counseling ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; methods

OBJECTIVETo assess the value of G-banded karyotyping in combination with multiplex ligation-dependent probe amplification (MLPA) as a tool for the detection of chromosomal abnormalities in fetuses with congenital heart defects.

METHODSThe combined method was used to analyze 104 fetuses with heart malformations identified by ultrasonography. Abnormal findings were confirmed with chromosomal microarray analysis (CMA).

RESULTSNineteen (18%) fetuses were found to harbor chromosomal aberrations by G-banded karyotyping and MLPA. For 93 cases, CMA has detected abnormalities in 14 cases including 10 pathogenic copy number variations (CNVs) and 4 CNVs of uncertain significance (VOUS). MLPA was able to detect all of the pathogenic CNVs and 1 VOUS CNV.

CONCLUSIONCombined use of G-banded karyotyping and MLPA is a rapid, low-cost and effective method to detect chromosomal abnormalities in fetuses with various heart malformations.

Chromosome Aberrations ; Chromosome Banding ; Chromosome Disorders ; diagnosis ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Genetic Testing ; methods ; Heart Defects, Congenital ; diagnosis ; genetics ; Humans ; Karyotyping ; methods ; Multiplex Polymerase Chain Reaction ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVETo explore the pathogenesis of a child with growth retardation, liver damage and congenital heart disease.

METHODSG-banded chromosomal karyotyping, high-throughput next-generation sequencing (HT-NGS)and fluorescence in situ hybridization(FISH) were used to characterize the structural chromosomal aberration.

RESULTSThe child was found to have a karyotype of 46, XX, t(1;2) (q25;q21), t(7;20) (q21;p13). HT-NGS has detected a microdeletion at 2q21.3 and 7q21.11, respectively, which were verified by FISH.

CONCLUSIONCombined cytogenetic and molecular analysis can detect chromosome micrdeletions more precisely. The abnormalities of the child may be attributed to heterozygous deletion of ZEB2, ABCB4 and SEMA3A genes.

Chromosome Aberrations ; Chromosome Banding ; methods ; Female ; Heart Defects, Congenital ; genetics ; Humans ; Infant ; Intellectual Disability ; genetics ; Karyotyping ; methods ; Liver Diseases ; genetics

OBJECTIVETo report on clinical and laboratory features of myeloid neoplasms with double del(20q).

METHODSCytogenetic examination of bone marrow was performed on 13 cases of myeloid neophasms with double del(20q) after 24 hours of cell culture. R-banding was used to analyze the karyotypes. Interphase fluorescence in situ hybridization (FISH) was performed using dual-color probes for 20q11/20q12.

RESULTSDouble del(20q) was found to be the sole abnormality in 9 cases, double del(20q) and trisomy 9 was found in 1 case, trisomy del(20q) was found in 1 case, and sole del(20q) clone and double del(20q) clone were found to coexist in 2 cases. In 10 cases, interphase FISH showed one green and one red signal in cells with del(20q), which indicated deletion of both 20q11 and 20q12. Immunophenotyping of the leukemia cells showed positiveness for CD13 and/or CD33, CD117 in all 9 cases. Among these, co-expression of CD34 and/or HLA-DR was found in 6 cases, and coexpression of CD3 and CD7 was found in 1 case. Of the 13 cases, there were one AML-M6, nine MDS, one pure amegalokaryocye aplastic thrombocytopenia, one with normal morphology of bone marrow, and one undetermined due to dilution of the bone marrow by blood. Cytopenia were found in all cases. 9 of 13 cases died, and 4 survived with a median survival of 9 months.

CONCLUSIONDouble del(20q) is a rare but recurrent chromosomal abnormality derived from del(20q). It has unique clinical and laboratory features, and the prognosis is poor.

Aged ; Chromosome Banding ; methods ; Chromosome Deletion ; Female ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; Neoplasms ; genetics

OBJECTIVETo explore the genetic cause of a female patient with severe mental retardation and a history of adverse pregnancy.

METHODSThe patient was subjected to G-banded chromosome analysis and single nucleotide polymorphism array (SNP-array) assaying. The correlation between genomic variations and the phenotype was explored.

RESULTSThe patient was found to have a complex chromosome rearrangement involving 5 chromosomes. The karyotypes of her parents were both normal. SNP-array assay has identified a 1.6 Mb microdeletion at chromosome 15q21.3 which involved 15 RefSeq genes and a 0.5 Mb microdeletion at 5q21.1 which involved one RefSeq gene.

CONCLUSIONThe microdeletions, which involved TCF12, ADMA10 and AQP9 genes, probably underlie the mental retardation shown by the patient.

Adult ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Intellectual Disability ; genetics ; Karyotype