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

OBJECTIVE: To investigate the clinical and laboratory characteristics of hematopoietic tumor with t(5;12)(q33;p13). To sum up the similarities and differences of these diseases. METHODS: The chromosome samples were prepared by short-term training of bone marrow cells, and the karyotype analysis was carried out by R or G band. Using PDGFRb dual color fracture rearrangement probe and fluorescence in situ hybridization (FISH) technology to detect the rearrangement of the gene, the immune-typing analysis was performed using flow cytometry. For 7 cases with t(5;12)(q33;p13) patients with hematopathy were retrospectively analyzed. RESULTS: Seven patients were diagnosed with different diagnoses, mainly male. Nuclear type analysis 5 cases of t(5;12)(q33;p13) was of primary abnormality and 2 cases of secondary abnormality. Five of the seven patients were treated and two untreated. Among the treatment patients, two cases were fatal, two case was lost and one case was treated with combined chemotherapy with dasatinib targeted therapy. The treatment process was successful and is still in hospital. CONCLUSION With t (5;12) (q33;p13) blood system tumors are rare and have unique clinical and laboratory characteristics. At the same time, the heterogeneity is obvious, the patients with tyrosine kinase inhibitor combined with chemotherapy have good effect and good prognosis, and the prognosis of chemotherapy alone is poor.
Chromosomes, Human, Pair 12 ; genetics ; Chromosomes, Human, Pair 5 ; genetics ; Hematologic Neoplasms ; genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Retrospective Studies ; Translocation, Genetic

OBJECTIVETo screen for genomic copy number variants (CNVs) in a fetus with one sibling affected with Prader-Willi syndrome using single nucleotide polymorphism (SNP) array.

METHODSThe fetus and its parents were subjected to chromosomal karyotyping and SNP array analysis.

RESULTSA 5p15.33 microdeletions was identified in the fetus and its phenotypically normal mother with a size of 344 kb (113 576 to 457 213). The father was normal for both testing. Analysis of literature and CNVs database indicated the above CNV to be variant of unclear significance. The couple decided to continue with the pregnancy and gave birth to a healthy boy at full-term. No abnormalities were found during the follow-up.

CONCLUSIONThis study may provide further data for the phenotype-genotype correlation of 5p15.33 microdeletion, which differs from Cri du Chat syndrome.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Male ; Prader-Willi Syndrome ; diagnosis ; embryology ; genetics ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo use combined G-banding and array-comparative genomic hybridization (aCGH) for the prenatal diagnosis of a fetus with 5q35 deletion syndrome.

METHODSChromosomal karotypes of the fetus and parents were analyzed with G-banding analysis. aCGH was performed to detect minor chromosomal structural abnormalities.

RESULTSThe karyotype of the fetus was ascertained as 46, XY, t(5;10)(q35;p13), and the karyotypes of the parents were normal. aCGH has identified a de novo 1.68 Mb deletion at 5q35.2q35.3 and a 1.44 Mb duplication at 10p14p13.

CONCLUSIONaCGH has a higher resolution and greater accuracy for mapping chromosomal aberrations and is a useful supplement for G banding karyptyping analysis.

Adult ; Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; genetics ; Comparative Genomic Hybridization ; Cri-du-Chat Syndrome ; diagnosis ; embryology ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Karyotyping ; Male ; Prenatal Diagnosis ; Trisomy ; diagnosis ; 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*

5p deletion syndrome, also known as Cri-du-Chat syndrome, is a chromosomal abnormality caused by a deletion in the short arm of chromosome 5. Clinical features of 5p deletion syndrome are difficult to identify prenatally by ultrasound examination, thus most cases of 5p deletion syndrome have been diagnosed postnatally. Here, we report eight cases of 5p deletion syndrome diagnosed prenatally, but were unable to find common prenatal ultrasound findings among these cases. However, we found that several cases of 5p deletion syndrome were confirmed prenatally when karyotyping was performed on the basis of abnormal findings in a prenatal ultrasound scan. Hence, it is necessary to carefully perform prenatal ultrasonography for detection of rarer chromosomal abnormalities as well as common aneuploidy.
Aneuploidy ; Arm ; Chromosome Aberrations ; Chromosomes, Human, Pair 5 ; Cri-du-Chat Syndrome* ; Karyotyping ; Prenatal Diagnosis* ; Ultrasonography ; Ultrasonography, Prenatal