OBJECTIVE: To delineate the origin and content of a mosaicism small supernumerary marker chromosome (sSMC) in a fetus with combined chromosomal karyotyping, chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH). METHODS: The fetus of a 31-year-old pregnant woman who had presented at the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City in 2022 was selected as the study subject. Non-invasive prenatal testing suggested that the fetus has harbored a 8.75 Mb duplication in 4q12q13.1. With informed consent, amniotic fluid and peripheral blood samples were taken from the couple for chromosomal karyotyping analysis. The origin and content of a sSMC was identified by CMA, and its proportion in amniotic fluid was determined with a FISH assay. RESULTS: The karyotypes of the pregnant woman, her husband and the fetus were respectively determined as 46,XX, 46,XY,inv(9)(p12q12), and 47,XY,inv(9)(p12q12)pat,+mar[75]/ 46,XY,inv(9)(p12q12)pat[25]. CMA test of the amniotic fluid sample was arr[hg19]4p11q13.1(48978053_63145931)×3, which revealed no mosaicism. However, FISH analysis showed that 59% of interphase cells from the cultured amniotic fluid sample had contained three signals for the centromere of chromosome 4, whilst 65% of interphase cells from the re-sampled amniotic fluid had three such signals, which confirmed the existence of trisomy 8 mosaicism. CONCLUSION Chromosomal structural abnormality combined with mosaicism can be delineated with combined chromosomal karyotyping and molecular techniques such as FISH and CMA, which has enabled more accurate counseling for the family.
Humans ; Child ; Female ; Pregnancy ; Adult ; In Situ Hybridization, Fluorescence ; Mosaicism ; Genetic Techniques ; Amniotic Fluid ; Chromosomes, Human, Pair 4

OBJECTIVE: To investigate the clinical features of fetuses with Wolf-Hirschhorn syndrome(WHS) and explore the diagnostic methods and prenatal ultrasound characteristics and provide evidence for prenatal genetic counseling. METHODS: We retrospectively analyzed 5 cases of WHS fetuses diagnosed from March 2016 to February 2020, and analyzed the results of chromosomal karyotype analysis and chromosomal microarray analysis (CMA) of the fetuses. RESULTS: Five cases of WHS were detected by CMA, four cases were detected by karyotype analysis. Prenatal ultrasound revealed 4 abnormalities, of which 3 had intrauterine growth restriction, and only 1 had abnormalities of the maxillofacial region. The sequence of the fragments was 4p16.3p16.1 with a loss of 6.5 Mb, 4p16.3p15.32 with a loss of 15.6 Mb combined with 2p25.3 increased by 906kb, 4p16.3p15.31 with a loss of 20.4 Mb, 4p16.p15.1 with a loss of 35 Mb and 4p16.3p14 with a loss of 37 Mb. CONCLUSION Fetal growth restriction may be one of the early manifestations of WHS. Absence of fetal facial abnormality by prenatal ultrasound screening cannot exclude WHS. Karyotype analysis may miss the diagnosis of WHS, while combined CMA techniques can improve the diagnostic accuracy.
Chromosomes, Human, Pair 4/genetics* ; Female ; Fetal Growth Retardation/genetics* ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis ; Retrospective Studies ; Wolf-Hirschhorn Syndrome/genetics*

OBJECTIVE: To explore the genetic basis for a child featuring delayed intellectual development. METHODS: The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array (SNP-array) analysis. Suspected copy number variations (CNVs) were verified in both parents. RESULTS: No karyotypic abnormality was found with the child and his parents. SNP-array results for both parents were normal. The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52 957 042-53 129 237. The deletion only involved one OMIM gene, namely TCF4, resulting in removal of its exons 6 to 8. CONCLUSION The SNP-array assay has facilitated with the diagnosis of this child. Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome (PTHS) in this patient.
Child ; Chromosome Deletion ; Chromosomes, Human, Pair 18 ; genetics ; DNA Copy Number Variations ; Developmental Disabilities ; genetics ; Facies ; Humans ; Hyperventilation ; genetics ; Intellectual Disability ; genetics ; Phenotype ; Transcription Factor 4 ; genetics

OBJECTIVE: To explore the nature and origin of chromosomal copy number variants (CNVs) in a pedigree affected with mental retardation. METHODS: Genomic CNVs of the proband were analyzed by next generation sequencing (NGS). Chromosomal karyotypes of the proband and his relatives were analyzed with high-resolution karyotyping and fluorescence in situ hybridization (FISH). RESULTS: Clinical phenotypes of the proband and other patients from the pedigree included mental retardation and mild dysmorphism. The results of NGS revealed that the proband carried a 16.24 Mb microduplication at 4p16.3-15.32 and a 2.2 Mb microdeletion at 8p23.3-23.2. Other patients of the pedigree harbored the same variants, while those without the phenotypes did not harbor the variants. The results of high-resolution karyotyping and FISH revealed that the mother of the proband carried a reciprocal translocation between 4p and 8p, and her karyotype was 46,XX,t(4;8)(p16;p23). No karyotypic abnormality was detected in his father. CONCLUSION The abnormal phenotypes of this pedigree may be attributed to 4p microduplication in conjunct with 8p microdeletion derived from a maternal balanced translocation between 4p and 8p.
Chromosome Aberrations ; Chromosome Duplication ; Chromosomes, Human, Pair 4 ; Chromosomes, Human, Pair 8 ; Female ; Genetic Testing ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Pedigree ; Phenotype

OBJECTIVE: To make molecular diagnosis of an infant affected with severe developmental delay and multiple birth defects, assisting prenatal diagnosis for the second pregnancy. METHODS: Standard G-banded karyotyping was performed for the fetus and his parents. Single nucleotide polymorphism array (SNP array) was used to detect submicroscopic chromosomal aberration. Fluorescence in situ hybridization (FISH) was employed to determine the parental origin of the aberration. RESULTS: Both the proband and the fetus harbored a 5.4 Mb distal 4p deletion and a 6.9 Mb distal 6q duplication. FISH confirmed that the mother has carried a balanced translocation involving 4p and 6q. CONCLUSION The unbalanced chromosomal aberration in the proband and the fetus were both derived from the mother. Both patients showed a Wolf-Hirschhorn syndrom phenotype and partial phenotype of 6q trisomy. SNP array combined with FISH are essential for the detection of cryptic chromosomal aberrations which may be missed by coventional karyotyping analysis.
Chromosomes, Human, Pair 4 ; genetics ; Chromosomes, Human, Pair 6 ; genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Karyotyping ; Male ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Translocation, Genetic ; Wolf-Hirschhorn Syndrome ; genetics

The 4p deletion syndrome, also known as Wolf-Hirschhorn syndrome, is a well-known genetic disorder caused by a partial deletion of the short arm of chromosome 4. The great variability in the extent of the 4p deletion and the possible contribution of additional genetic rearrangements leads to a wide spectrum of clinical manifestations. Herein, we present our experience with eight cases of 4p deletion syndrome, ascertained prenatally between 1998 and 2016 at our hospital.
Arm ; Chromosomes, Human, Pair 4 ; Prenatal Diagnosis* ; Wolf-Hirschhorn Syndrome*

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

No abstract available.
Adolescent ; Chromosomes, Human, Pair 11 ; Chromosomes, Human, Pair 4 ; Gene Rearrangement ; Histone-Lysine N-Methyltransferase/*genetics ; Humans ; Male ; Myeloid-Lymphoid Leukemia Protein/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics

BACKGROUND: We comprehensively profiled cytogenetic abnormalities in multiple myeloma (MM) and analyzed the relationship between cytogenetic abnormalities of undetermined prognostic significance and established prognostic factors. METHODS: The karyotype of 333 newly diagnosed MM cases was analyzed in association with established prognostic factors. Survival analysis was also performed. RESULTS: MM with abnormal karyotypes (41.1%) exhibited high international scoring system (ISS) stage, frequent IgA type, elevated IgG or IgA levels, elevated calcium levels, elevated creatine (Cr) levels, elevated β2-microglobulin levels, and decreased Hb levels. Structural abnormalities in chromosomes 1q, 4, and 13 were independently associated with elevated levels of IgG or IgA, calcium, and Cr, respectively. Chromosome 13 abnormalities were associated with poor prognosis and decreased overall survival. CONCLUSIONS: This is the first study to demonstrate that abnormalities in chromosomes 1q, 4, and 13 are associated with established factors for poor prognosis, irrespective of the presence of other concurrent chromosomal abnormalities. Chromosome 13 abnormalities have a prognostic impact on overall survival in association with elevated Cr levels. Frequent centromeric breakpoints appear to be related to MM pathogenesis.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Calcium/blood ; *Chromosome Aberrations ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 4 ; Creatine/blood ; Female ; Hemoglobins/analysis ; Humans ; Immunoglobulin A/blood ; Immunoglobulin G/blood ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/genetics/mortality ; Multivariate Analysis ; Prognosis ; Survival Rate ; Young Adult

No abstract available.
Child ; Chromosome Banding ; *Chromosome Deletion ; Chromosomes, Human, Pair 4/*genetics ; Comparative Genomic Hybridization ; Developmental Disabilities/diagnosis/*genetics ; Humans ; Male ; Sequence Deletion