OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with intellectual disability (ID), developmental delay (DD), and autistic spectrum disorder (ASD). METHODS: Forty patients with ID/DD/ASD referred to Nanshan Maternity and Child Health Care Hospital from September 2018 to January 2022 were enrolled. G-banded karyotyping analysis was carried out for the patients. Genomic DNA was extracted from peripheral blood samples and subjected to CNV-Seq analysis to detect chromosome copy number variations (CNVs) in such patients. ClinVar, DECIPHER, OMIM and other database were searched for data annotation. RESULTS: Among the 40 patients (including 30 males and 10 females), 16, 15 and 6 were diagnosed with ID, DD and ASD, respectively. One patient had combined symptoms of ID and DD, whilst the remaining two had combined ID and ASD. Four patients were found with abnormal karyotypes, including 47,XY,+mar, 46,XY,inv(8)(p11.2q21.2), 46,XX,del(5)(p14) and 46,XX[76]/46,X,dup(X)(p21.1q12). Chromosome polymorphism was also found in two other patients. CNV-seq analysis has detected 32 CNVs in 20 patients (50.0%, 20/40). Pathogenic CNVs were found in 10 patients (25.0%), 15 CNVs of uncertain clinical significance were found in 12 patients (30.0%), and 7 likely benign CNVs were found in 4 patients (10.0%). CONCLUSION Chromosome CNVs play an important role in the pathogenesis of ID/DD/ASD. CNV-seq can detect chromosomal abnormalities including microdeletions and microduplications, which could provide a powerful tool for revealing the genetic etiology of ID/DD/ASD patients.
Pregnancy ; Child ; Male ; Humans ; Female ; DNA Copy Number Variations ; Intellectual Disability/genetics* ; Autism Spectrum Disorder/genetics* ; Developmental Disabilities/genetics* ; Abnormal Karyotype

OBJECTIVE: To investigate the expression level of vascular endothelial growth factor (VEGF) in serum of patients with multiple myeloma (MM) and its possible clinical significance. METHODS: 68 patients with MM who were admitted to The First Affiliated Hospital of Bengbu Medical College from July 2019 to June 2020 were collected. The expression level of VEGF was detected by VEGF enzyme-linked immunosorbent assay, the correlation of VEGF expression with serous effusion in MM was explored, and the relationship between VEGF expression level and clinical features and prognosis of patients with MM was analyzed. RESULTS: The positive rate of VEGF was 36.76% (25/68) in 68 patients with MM, 10 cases (58.82%, 10/17) were VEGF positive in 17 MM patients with serous effusion. The expression level of VEGF in patients with positive serous effusion was significantly higher than that in patients with negative serous effusion (P<0.05); the expression level of VEGF in MM patients of the newly diagnosed and untreated group was significantly higher than that in the remission group after treatment (P<0.05), but there was no significant difference in the expression level of VEGF between the newly diagnosed group and the refractory/relapsed (R/R) group (P>0.05). Among 68 patients with MM, 48 patients underwent FISH examination, 28 cases had normal karyotype (58.33%), and 20 cases had abnormal karyotype (41.67%). The abnormal karyotype was mainly IgH rearrangement, with a total of 10 cases (20.83%); other cases: 1q21+, del (13q14), del (17p13) were 3 cases (6.25%), 2 cases (4.17%), 7 cases (14.58%), respectively. Compared with VEGF^- group, the incidence of IgH rearrangement and del (17p13) in VEGF⁺ group was higher [IgH rearrangement: 35% vs 10.71%, P=0.043; del(17p13): 30% vs 3.57%, P=0.011]. Compared with negative serous effusion group, the incidence of del (17p13) in positive serous effusion group was higher (31.25% vs 6.25%, P=0.021). The proportion of patients with positive VEGF and serous effusion was 14.71% (10/68), and the proportion of patients with negative VEGF and negative serous effusion was 52.94% (36/68). There was a correlation between serous effusion and VEGF expression (r=0.264, P=0.029). CONCLUSION The prognosis of MM patients with serous effusion is poor, and the expression of VEGF in serum of these patients is significantly high. The increased VEGF may be involved in the occurrence and development of serous effusion.
Abnormal Karyotype ; Chromosome Aberrations ; Chromosome Deletion ; Humans ; In Situ Hybridization, Fluorescence ; Multiple Myeloma/drug therapy* ; Vascular Endothelial Growth Factor A

Background: The 47,XYY syndrome could result in fertility problems. However, seldom studies reported comprehensive researches on the embryonic development and pregnancy outcomes of these patients. This study aimed to evaluate the clinical outcomes of nonmosaic 47,XYY patients performed with fluorescent in situ hybridization (FISH) and preimplantation genetic diagnosis (PGD) treatment. Methods: This was a retrospective study. Between January 2012 and May 2017, 51 infertile males with nonmosaic 47,XYY syndrome underwent FISH-PGD were included in the study. According to sex chromosomal FISH results, embryos were classified as normal signal, no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups, respectively. The incidence of each group, the fixation rate, and hybridization rate were calculated. Embryonic development and pregnancy outcomes were also analyzed. The measurement data were analyzed with Student's t-test. The comparison of categorical data was analyzed with the Chi-square test and Fisher's exact test when expected cell count was <5. Results: The 53 PGD cycles with 433 embryos were analyzed. The fixation rate was 89.6%, while the hybridization rate was 96.4%. There were 283 embryos with two sex chromosomal signals with clear diagnosis (65.4%). The numbers of no nuclei fixed, no signal in fixed nuclei, suspensive signal, and abnormal signal groups were 45 (10.4%), 14 (3.2%), 24 (5.5%), and 67 (15.5%), respectively. Embryos with abnormal signals were abandoned. The number of good-quality embryos was 210 (57.4%), including implanted embryos on day 4/day 5 and cryopreserved. The rates of good-quality embryos in the no nuclei fixed (22.2%), no signal in fixed nuclei (28.6%), and suspensive signal groups (33.3%) were comparable (P > 0.05), and were significantly lower than the normal signal group (66.4%, P < 0.001). The clinical pregnancy rates of fresh and frozen embryos transferred cycles were 70.6% and 85.7%, respectively. Conclusions Among embryos with a clear diagnosis of sex chromosome, about one-fifth showed abnormal signals. Embryos with two sex chromosomal signals are more likely to develop into good-quality ones. The application of the PGD by FISH may help to improve the clinical outcome s.
Female ; Humans ; In Situ Hybridization, Fluorescence ; Infertility, Male ; genetics ; Male ; Pregnancy ; Preimplantation Diagnosis ; Retrospective Studies ; Sex Chromosome Disorders ; diagnosis ; genetics ; XYY Karyotype ; diagnosis ; genetics

BACKGROUND: The identification of genetic abnormalities in patients with multiple myeloma (MM) has gained emphasis because genetics-based risk stratification significantly affects overall survival (OS). We investigated genetic abnormalities using conventional cytogenetics and FISH and analyzed the prognostic significance of the identified additional abnormalities in MM. METHODS: In total, 267 bone marrow samples were collected from February 2006 to November 2013 from patients who were newly diagnosed as having MM in a tertiary-care hospital in Korea. The clinical and laboratory data were retrospectively obtained. Cox proportional hazard regression was used to examine the relationship between clinical/genetic factors and survival outcome, using univariate and multivariate models. RESULTS: Using conventional cytogenetic analysis and FISH, 45% (120/267) and 69% (183/267) patients, respectively, were identified to harbor genetic abnormalities. In the univariate analysis, the following genetic variables were identified to affect OS: abnormal karyotype (P < 0.001), aneuploidy (P=0.046), −13 or del(13q) (P=0.002), 1q amplification (P < 0.001), and t(4;14) (P=0.020). In the multivariate analysis, the presence of −13 or del(13q) was the only significant genetic factor affecting OS (P=0.012) with a hazard ratio (HR) of 2.131 (95% confidence interval [CI], 1.185–3.832) in addition to the clinical factor of age (>65 years) (P=0.013) with an HR of 2.505 (95% CI, 1.218–5.151). CONCLUSIONS: Our findings highlight the importance of applying a comprehensive approach for detecting genetic abnormalities, which could be closely associated with the prognostic significance of MM.
Abnormal Karyotype ; Aneuploidy ; Bone Marrow ; Cytogenetic Analysis ; Cytogenetics ; Humans ; Korea ; Multiple Myeloma* ; Multivariate Analysis ; Prognosis ; Retrospective Studies

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

Neuroblastomas are sometimes associated with abnormal constitutional karyotypes, but the XYY karyotype has been rarely described in neuroblastomas. Here, we report a case of an esthesioneuroblastoma in a boy with a 47, XYY karyotype. A 6-year-old boy was admitted to our hospital because of nasal obstruction and palpable cervical lymph node, which he first noticed several days previously. A polypoid mass in the right nasal cavity was detected through sinuscopy. Biopsy of the right nasal polyp was performed. Based on the result, the patient was diagnosed with a high-grade esthesioneuroblastoma. Nuclear imaging revealed increased uptake in both the right posterior nasal cavity and the right cervical IB-II space, suggesting metastatic lymph nodes. Cytogenetic analysis revealed a 47, XYY karyotype. Twelve courses of concurrent chemotherapy were administered. Three years after the completion of chemotherapy, the patient had had no disease recurrence. He manifested behavioral violence and temper tantrums, so we started methylphenidate for correction of the behavior.
Biopsy ; Child ; Chromosome Aberrations ; Cytogenetic Analysis ; Drug Therapy ; Esthesioneuroblastoma, Olfactory* ; Humans ; Karyotype ; Lymph Nodes ; Male* ; Methylphenidate ; Nasal Cavity ; Nasal Obstruction ; Nasal Polyps ; Neuroblastoma ; Recurrence ; Violence ; XYY Karyotype*

OBJECTIVETo explore the genetic cause for a boy featuring mainly with mental retardation.

METHODSG-banding karyotyping and fluorescence in situ hybridization (FISH) were carried out for the child and his parents. The child was also analyzed with chromosome microarray (CMA). Suspected microdeletion was validated with quantitative PCR.

RESULTSThe proband was found to have a 47,XYY karyotype by both chromosome and FISH analyses, while both of his parents had a normal karyotype. CMA suggested that the proband had one copy of X chromosome and two copies of Y chromosome. In addition, CMA has also detected deletion of the KYNU gene (mapped at 2q22.2), which could be pathogenic. The result was confirmed by qPCR.

CONCLUSIONFor its high resolution, CMA can be used to identify potential microdeletion/duplications among children with chromosome aneuploidy and unusual phenotypes.

Adult ; Child, Preschool ; Chromosome Banding ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Intellectual Disability ; genetics ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide ; Sex Chromosome Disorders ; diagnosis ; genetics ; XYY Karyotype ; diagnosis ; genetics

OBJECTIVETo explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.

METHODSR- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.

RESULTSOf 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

CONCLUSIONChromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.

Abnormal Karyotype ; Acute Disease ; Anemia, Refractory, with Excess of Blasts ; Bone Marrow ; China ; Chromosome Aberrations ; Chromosome Banding ; Chromosomes, Human, Pair 1 ; genetics ; Humans ; Karyotyping ; Leukemia ; diagnosis ; genetics ; Myelodysplastic Syndromes ; diagnosis ; genetics ; Prognosis ; Risk Factors ; Trisomy

OBJECTIVETo investigate the relationship between cytogenetic markers with World Health Organization (WHO) classification, disease progress and prognosis in cases with primary myelodysplastic syndromes (MDS).

METHODS298 patients with de novo MDS from the first affiliated hospital of medical school, Zhejiang University were enrolled in the retrospective analysis of WHO classification, karyotype, and prognosis. Follow-up study was also conducted.

RESULTSThe WHO classifications at first diagnosis were as follows: refractory cytopenia with unilineage dysplasia (RCUD), 18 cases; refractory anemia with ring sideroblasts (RARS), 8 cases; refractory cytopenia with multiline dysplasia (RCMD), 104 cases; refractory anemia with excess blasts-1, 76 cases; refractory anemia with excess blasts-2, 85 cases; MDS unclassified (MDS-U), 5 cases involved; and single del (5q), 2 cases. 39.6% of MDS patients carried karyotypic abnormalities. Among them, the frequency of numerical abnormalities, structural abnormalities and the existence of composite abnormalities were 45, 31, and 42, respectively. The composite abnormalities were unbalanced translocations and complex chromosomal abnormalities. The incidence of both karyotypic abnormalities and complex chromosomal abnormalities in RAEB group was higher than that in non-RAEB group (P<0. 05). An analysis based on IPSS-R Scoring System showed that advanced risk stratification (except the low-risk group) gradually enhanced the incidence of karyotypic abnormalities (P<0.05). In addition, the probability of evolution to leukemia increased with the higher IPSS-R score (P<0.05). In RAEB group, the cases with +8 chromosome, accounting for 19.5% of karyotypic abnormalities, had worse prognosis than those with normal chromosomes.

CONCLUSIONKaryotype was identified with an independent risk factor in MDS patients. Therefore, the information on cytogenetic analysis was critical for diagnosis, prognosis and individual treatment. MDS patients presenting+8 chromosome, an intermediate risk factor, were associated with a poorer outcome compared to cases with normal chromosomes in RAEB group.

Abnormal Karyotype ; Anemia, Refractory ; Chromosome Aberrations ; Chromosomes, Human, Pair 8 ; Follow-Up Studies ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis ; Retrospective Studies ; Risk Factors ; World Health Organization

OBJECTIVETo explore the prognostic significance of monosomal karyotype (MK) in patients with acute myeloid leukemia (AML).

METHODSThe clinical data of 498 AML patients were analyzed retrospectively.

RESULTSOf the 498 patients, 233 (46.8%) cases had an abnormal karyotype. 42 patients fulfilled the criteria for MK, which were 8.4% of all cases and 18.0% of patients with abnormal karyotype, respectively. The most frequent autosomal monosomies were -7 and -17. 70 patients had complex karyotype (CK), in all patients and patients with abnormal karyotype accounted for 14.1% and 30.0%, respectively. Patients with MK were associated with significantly older (median age 62.5 vs 52 years, P=0.003), and lower HGB concentrations (62.5 vs 77 g/L, P=0.009) and lower WBC counts (7.0×10⁹/L vs 11.7×10⁹/L, P=0.008). Among MK cases, the most frequent chromosome abnormalities were complex karyotype, -7, -5, 7q-, and 5q-. In univariate analysis, MK patients had worse survival than those without MK (7.3 months vs 26.3 months, P<0.001). CK patients also had poorer outcomes than patients without CK (14.8 months vs 26.3 months, P<0.001). In CK patients, survival was worse in MK patients than patients without MK (7.4 months vs 19.2 months, P=0.007). By COX analysis, MK was an independent prognostic factor, beyond NCCN criteria and CK [HR=2.610 (1.632-4.175), P<0.001].

CONCLUSIONMK was an independent adverse prognostic factor in AML patients.

Abnormal Karyotype ; Humans ; Karyotyping ; Leukemia, Myeloid, Acute ; Monosomy ; Prognosis ; Retrospective Studies