OBJECTIVE: To validate a fetus with high risk for trisomy 13 suggested by non-invasive prenatal testing (NIPT). METHODS: The fetus was selected as the study subject after the NIPT detection at Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences on February 18, 2019. Clinical data of the pregnant woman was collected. Fluorescence in situ hybridization (FISH), chromosomal karyotyping analysis and chromosomal microarray analysis (CMA) were carried out on amniotic fluid and umbilical cord blood and the couple's peripheral blood samples. Copy number variation sequencing (CNV-seq) was also performed on the placental and amniotic fluid samples following induced labor. RESULTS: The pregnant woman, a 38-year-old G4P1 gravida, was found to have abnormal fetal development by prenatal ultrasonography. NIPT test suggested that the fetus has a high risk for trisomy 13. Chromosomal karyotyping analysis of fetal amniotic fluid and umbilical cord blood were 46,XN,add(13)(p10). The result of CMA was arr[hg19]1q41q44(223937972_249224684)×3, with the size of the repeat fragment being approximately 25.29 Mb, the fetal karyotype was thereby revised as 46,XN,der(13)t(1;13)(q41;p10). Chromosomal karyotyping analysis and CMA of the parents' peripheral blood samples showed no obvious abnormality. The CNV-seq analysis of induced placenta revealed mosaicisms of normal karyotype and trisomy 13. The CNV-seq test of induced amniotic fluid confirmed a duplication of chr1:22446001_249220000 region spanning approximately 24.75 Mb, which was in keeping with the CMA results of amniotic fluid and umbilical cord blood samples. CONCLUSION NIPT may yield false positive result due to placenta mosaicism. Invasive prenatal diagnosis should be recommended to women with a high risk by NIPT test. And analysis of placenta can explain the inconsistency between the results of NIPT and invasive prenatal diagnosis.
Humans ; Female ; Pregnancy ; Trisomy 13 Syndrome/genetics* ; DNA Copy Number Variations ; Placenta ; Chromosomes, Human, Pair 1 ; In Situ Hybridization, Fluorescence ; Prenatal Diagnosis/methods* ; Fetus ; Amniotic Fluid ; Chromosome Aberrations ; Trisomy/genetics*

OBJECTIVE: To carry out cyto- and molecular genetic analysis for a fetus with a ring chromosome identified through non-invasive prenatal testing (NIPT). METHODS: A pregnant woman presented at the Shengjing Hospital Affiliated to China Medical University on May 11, 2021 was selected as the study subject. Maternal peripheral blood sample was screened by NIPT, and G-banded chromosomal karyotyping was carried out on amniotic fluid and peripheral blood samples from the couple. The fetus and the pregnant woman were also subjected to genomic copy number variation sequencing (CNV-seq), chromosomal microarray analysis (CMA), and fluorescence in situ hybridization (FISH) assay. RESULTS: NIPT result suggested that the fetus had monomeric mosaicism or fragment deletion on chromosome 13. G banded chromosomal analysis showed that both the fetus and its mother had a karyotype of 47,XX,der(13)(pter→p11::q22→q10),+r(13)(::p10::q22→qter::), whilst her husband had a normal karyotype. FISH has verified the above results. No abnormality was detected with CNV-seq and CMA in both the fetus and the pregnant woman. CONCLUSION The ring chromosome 13 in the fetus has derived from its mother without any deletion, duplication and mosaicism. Both the fetus and the pregnant woman were phenotypically normal.
Humans ; Pregnancy ; Female ; Ring Chromosomes ; Chromosomes, Human, Pair 13/genetics* ; In Situ Hybridization, Fluorescence ; DNA Copy Number Variations ; Prenatal Diagnosis/methods* ; Amniotic Fluid

OBJECTIVE: To analyze the clinical features and pathogenesis of a fetus with holoprosencephaly. METHODS: The findings of prenatal ultrasonography was reviewed. Following elective abortion, whole exome sequencing (WES) was carried out to identify potential pathogenic variant. Copy number variants (CNVs) of the abortus and its parents were detected by low-depth high-throughput sequencing. The parents were also analyzed by chromosomal karyotyping. RESULTS: Prenatal ultrasound suggested that the fetus had holoprosencephaly. WES revealed that it had approximately 33 Mb deletion at chromosome 13 involving ZIC2, a haploid dose sensitive gene. The results of low-depth high-throughput sequencing confirmed that the fetus carried a de novo 32.32 Mb deletion at 13q31.1-34. Karyotyping analysis has excluded gross chromosomal aberration in both parents. CONCLUSION The fetus was diagnosed with holoprosencephaly, which may be attributable to the 13q31.1-34 deletion involving the ZIC2 gene.
Adult ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Fetus ; Genetic Testing ; Holoprosencephaly ; diagnostic imaging ; genetics ; pathology ; Humans ; Karyotyping ; Male ; Nuclear Proteins ; genetics ; Pregnancy ; Prenatal Diagnosis ; Sequence Deletion ; Transcription Factors ; genetics ; Ultrasonography, Prenatal ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis of a child with congenital heart disease (CHD). METHODS: Clinical examination of the child was carried out. Chromosomal microarray analysis (CMA) and quantitative PCR were carried out to detect copy number variations. RESULTS: The major features of the child included CHD (ventricular septal defect, severe pulmonary hypertension, tricuspid regurgitation, patent ductus arteriosus, and patent foramen ovale), severe pneumonia and liver failure. A de novo 3.2 Mb deletion encompassing 25 genes in 13q34 and a paternal 2.2 Mb duplication in 19p13.3 were revealed by CMA and qPCR. CONCLUSION The 13q34 region probably contains susceptibility genes for CHD.
Child ; Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 13 ; DNA Copy Number Variations ; Heart Defects, Congenital ; Humans

OBJECTIVE: To determine the nature and origin of aberrant chromosomes in a child with multiple anomalies and psychomotor retardation. METHODS: Routine G-banding was carried out to analyze the karyotypes of the patient and his parents, and next generation sequencing for copy number variations (CNV-seq) was used for the fine mapping of the aberrant chromosomal regions. RESULTS: The proband and his uncle exhibited psychomotor retardation, craniofacial malformation, infantile external genitalia, and concealed penis. Cytogenetic analysis indicated that the child has a 46,XYqh+,+(9),t(9;13)(q13;q12),pat,-13 karyotype. His uncle was XYqh+,+(9),t(9;13)(q13;q12)mat,-13, his father was 46,XYqh+,t(9;13)(q13;q12)mat, his grandmother was 46,XX,t(9;13)(q13;q12), and his grandfather was 46,XYqh+. The result of CNV-seq assay for the child was 46,XY,+9p(pter-p13.2,-40 Mb×3). No deletion was detected. CONCLUSION The partial trisomy 9 and partial monosomy 13 probably underlie the phenotypic abnormalities in the child. Combined chromosomal karyotyping and DNA sequencing can facilitate delineation of the nature and origin of the aberrant chromosomes.
Abnormalities, Multiple ; Child ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 9 ; DNA Copy Number Variations ; Humans ; Karyotyping ; Male ; Monosomy ; Pedigree ; Translocation, Genetic ; Trisomy

A girl aged 5 months was admitted due to developmental delay. Physical examination showed delayed physical development, unusual facies (microcephalus, hypertelorism, low-set ears, wide nasal bridge, and short philtrum), and an absence of the labium minus at one side. The peripheral blood karyotype was 46,XX,r(13)(p11q33)[82]/45,XX,-13[10]/46,XX,r(13;13)(p11q33;p11q33)[8], and array-based comparative genomic hybridization showed an 87.5 Mb duplication in 13q11q33.2 region and an 8.2 Mb deletion in 13q33.2q34 region. Fluorescence in situ hybridization showed terminal depletion of the long arm of the ring chromosome 13. The girl was diagnosed with ring 13 syndrome. This syndrome has various clinical phenotypes and is closely associated with the amount and site of the loss of genetic material in chromosomal band and different rates of chimerism.
Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Comparative Genomic Hybridization ; Female ; Humans ; Infant ; Phenotype ; Ring Chromosomes ; Trisomy ; genetics

OBJECTIVE: To explore the characteristics of cytogenetics and molecular genetics in patients with multiple myeloma(MM). METHODS: Fluorescence in situ hybridization(FISH) was used for molecular genetics analysis in 86 cases of newly diagnosed MM, at the same time the chromosome karyotype analysis was performed in 20 cases. Specimen were bone marrow cells. RESULTS: FISH detection showed that 68 cases of MM (79.07%) had at least one type of the molecular genetic abnormalities. The positive rates of IgH rearrangement, 1q21 amplification, D13S319 deletion, RB1 deletion and.P53 deletion were 62.79%, 26.74%, 24.42% ,13.95% and 1.16%, respectively. The positive rate of IgH was significantly higher than that of any other probes(P<0.01). The positive rate of IgH was 79.41% in 68 cases. Out of which the positive rate of IgH single and combined with 1, 2, 3, 4 probes was 59.26%, 24.07%, 11.11%, 5.56% and 0 respectively. The positive rate of IgH only was very signficantly higher than that of combined with any other probes(P<0.01).The positive rate of 1q21 was 33.82% in 68 cases, Out of which the positive rates of 1q21 or combined with 1,2,3,4 probes was 21.74%, 43.48%, 21.74%,13.04% and 0 respectively, the 1q21 probe showed positive as combined with other probes(P<0.01), especially with IgH(P<0.05). The positive rates of D13S319 were 30.88% in 68 cases of patients, out of which the positive rates of D13S319 single or combined with 1, 2, 3, 4 probes was 14.29%, 28.57%, 42.86%, 14.29% and 0 respectively, the D13S319 combined with other probes appeared more significant positive(P<0.01), especially with 1 or 2 probes (P< 0.01). The positive rate of RB1 was 17.65% in 68 cases, the positive rate of RB1 singl or combined with 1, 2, 3, 4 probes were 0, 25%, 50%, 25% and 0, the RB1 appeared positive always combined with other probes, especially with D13S319 probe (P<0.01). The positive rate of P53 was 1.47%, as combined with RB1 and D13S319 probes. The chromosomal karyotyping showed that 3 cases carried abnormal chromosomal and 17 cases carried normal chromosome, Out of which 17 cases showed positive by FISH. There was a significant difference of sensitivity between FISH combined with chromosome karvotyping and single chromosome karvotype (P< 0.01). CONCLUSION The genetic abnormalies display obvious heterogenicity in MM. The sensitivity of FISH is higher than that of chromosomal karvotyping. If FISH and chromosome karvotyping are combined, the positive rate of abnormality can be raised.
Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma ; genetics ; Retrospective Studies

OBJECTIVETo explore the correlation between 13q33-q34 microdeletion and clinical phenotype.

METHODSRoutine chromosomal banding was performed to analyze the karyotype, while array-based comparative genomic hybridization (aCGH array) and single nucleotide polymorphism array(SNP array) were employed to investigate the genome copy number variations.

RESULTSThe karyotype of patient 1 was 46, XY, 9qh+,13qs. Patient 2 showed 46, XX, der (13). Patient 3 showed 46, XX, r(13) (p11.2q32) [43]/45, XX, 13[4]/46, XX, r(13;13) [2]/47, XX, 2r(13;13) [1]. Patient 4 did not undergo chromosome karyotyping analysis. Array analysis showed that four patients have different microdeletions in 13q33-34 region and had common features of 13q33-q34deletion including intellectual disability, facial dysmorphism, microcephaly, hypotonia, low birth weight and genital abnormality.

CONCLUSIONThe severity of phenotypes showed no correlation with the size of deletion in 13q33-q34. The lower percentage of patients with congenital heart disease suggested a complex pathogenesis of such disease. EFNB2, LIG4 and SOX1 in 13q33-34 region are promising candidates for mental retardation. LIG4 was also a likely candidate for microcephaly.

Child, Preschool ; Chromosome Banding ; methods ; Chromosome Deletion ; Chromosomes, Human, Pair 13 ; genetics ; Female ; Genetic Testing ; methods ; Humans ; Infant ; Intellectual Disability ; genetics ; Male

Chromosome Aberrations ; Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 17 ; Humans ; Multiple Myeloma ; genetics

No abstract available.
Chromosomes, Human, Pair 13 ; Chromosomes, Human, Pair 17 ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Fusion Proteins, bcr-abl/genetics ; Humans ; In Situ Hybridization, Fluorescence ; Karyotype ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology ; Retinoblastoma Binding Proteins/genetics ; *Translocation, Genetic ; Ubiquitin-Protein Ligases/genetics