OBJECTIVE: To understand clinical and laboratory characteristics of acute myeloid leukemia, myelodysplasia-related (AML-MR). METHODS: Blood sample of one patient with AML-MR admitted to our hospital in September 2021 was collected and synthetically analyzed by using techniques including complete blood cell count, peripheral blood and bone marrow cell morphology, bone marrow pathology and immunohistochemistry, hematology examination, flow cytometry (FCM), chromosome karyotype analysis and molecular pathology. The clinical and laboratory characteristics of AML-MR were analyzed and summarized according to the World Health Organization (WHO) standards. RESULTS: The patient showed pancytopenia and increased proportion of blasts in smear of peripheral blood cells. Bone marrow cytology and pathological examination showed significant proliferation of hematopoietic cells. Pathological immunohistochemistry showed increased expression of CD61, CD34, and CD117, while MPO, CD13, and CD33 were positive. FCM showed that abnormal myeloid progenitor cells accounted for approximately 18.61% of the total number of nuclear cells, with expression of CD34, CD13, CD117, HLA-DR, and CD33 (small amount). Additionally, 36.34% of the cells were primitive/immature red blood cells which expressed CD36, CD71, and CD117 (small amount). Chromosome karyotype analysis and molecular pathology detected three kinds of abnormalities including -5 and two kinds of TP53 related gene mutation, respectively. CONCLUSION AML-MR patient shows pancytopenia and increased proportion of blasts in smear of peripheral blood cells. Bone marrow cytology and pathological examination show significant proliferation of hematopoietic cells. FCM can detect myeloid progenitor cells and primitive/immature red blood cells, while chromosome karyotype analysis can detect three abnormal karyotypes.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Myelodysplastic Syndromes ; Flow Cytometry ; Karyotyping ; Male ; Middle Aged ; Mutation

Chromosome karyotyping is a critical way to diagnose various hematological malignancies and genetic diseases, of which chromosome detection in raw metaphase cell images is the most critical and challenging step. In this work, focusing on the joint optimization of chromosome localization and classification, we propose ChromTR to accurately detect and classify 24 classes of chromosomes in raw metaphase cell images. ChromTR incorporates semantic feature learning and class distribution learning into a unified DETR-based detection framework. Specifically, we first propose a Semantic Feature Learning Network (SFLN) for semantic feature extraction and chromosome foreground region segmentation with object-wise supervision. Next, we construct a Semantic-Aware Transformer (SAT) with two parallel encoders and a Semantic-Aware decoder to integrate global visual and semantic features. To provide a prediction with a precise chromosome number and category distribution, a Category Distribution Reasoning Module (CDRM) is built for foreground-background objects and chromosome class distribution reasoning. We evaluate ChromTR on 1404 newly collected R-band metaphase images and the public G-band dataset AutoKary2022. Our proposed ChromTR outperforms all previous chromosome detection methods with an average precision of 92.56% in R-band chromosome detection, surpassing the baseline method by 3.02%. In a clinical test, ChromTR is also confident in tackling normal and numerically abnormal karyotypes. When extended to the chromosome enumeration task, ChromTR also demonstrates state-of-the-art performances on R-band and G-band two metaphase image datasets. Given these superior performances to other methods, our proposed method has been applied to assist clinical karyotype diagnosis.
Humans ; Metaphase ; Karyotyping/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Chromosomes, Human/genetics*

Objective: To analyze the clinicopathological characteristics of 11 cases of chronic lymphocytic leukemia (CLL) with t (14;19) (q32;q13) . Methods: The case data of 11 patients with CLL with t (14;19) (q32;q13) in the chromosome karyotype analysis results of the Blood Diseases Hospital, Chinese Academy of Medical Sciences from January 1, 2018, to July 30, 2022, were retrospectively analyzed. Results: In all 11 patients, t (14;19) (q32;q13) involved IGH::BCL3 gene rearrangement, and most of them were accompanied by +12 or complex karyotype. An immunophenotypic score of 4-5 was found in 7 patients and 3 in 4 cases. We demonstrated that CLLs with t (14;19) (q32;q13) had a mutational pattern with recurrent mutations in NOTCH1 (3/7), FBXW7 (3/7), and KMT2D (2/7). The very-high-risk, high-risk, intermediate-risk, and low-risk groups consisted of 1, 1, 6, and 3 cases, respectively. Two patients died, 8 survived, and 2 were lost in follow-up. Four patients had disease progression or relapse during treatment. The median time to the first therapy was 1 month. Conclusion: t (14;19) (q32;q13), involving IGH::BCL3 gene rearrangement, is a rare recurrent cytogenetic abnormality in CLL, which is associated with a poor prognosis.
Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics* ; Retrospective Studies ; Translocation, Genetic ; Chromosome Aberrations ; Karyotyping

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

OBJECTIVE: To explore the genetic etiology for a child featuring mental retardation, language delay and autism. METHODS: G-banding chromosomal karyotyping and single nucleotide polymorphism array (SNP-array) were carried out for the child and her parents. RESULTS: The child was found to have a 46,XX,dup(8p?) karyotype, for which both of her parents were normal. SNP-array revealed that the child has harbored a 6.8 Mb deletion in 8p23.3p23.1 and a 21.8 Mb duplication in 8p23.1p12, both of which were verified as de novo pathogenic copy number variants. CONCLUSION The clinical features of the child may be attributed to the 8p deletion and duplication. SNP-array can facilitate genetic diagnosis for children featuring mental retardation in conjunct with other developmental anomalies.
Humans ; Child ; Pregnancy ; Female ; Intellectual Disability/genetics* ; Prenatal Diagnosis ; Karyotyping ; Chromosome Banding ; Chromosome Deletion

OBJECTIVE: To explore the genetic basis, clinical phenotype and pathogenesis for a child with mosaicism ring chromosome 4. METHODS: Clinical data of the child was collected. Peripheral blood chromosomal karyotype G banding analysis, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) were carried out for the child, in addition with a review of the literature. RESULTS: The child was born full-term with low birth weight, facial dysmorphism, patent ductus arteriosus and ventricular septal defect. His karyotype was determined as mos46,XY,r(4)(p16.3q35.2)[259]/45,XY,-4[25]/47,XY,r(4)(p16.3q35.2), +r(4)(p16.3q35.2)[8]/46,XY,der(4)del(4)(p16.3)inv(4)(p16.3q31.1)[6]/46,XY,dic?r(4;4)(p16.3q35.2;p16.3q35.2)[4]/48,XY,r(4)(p16.3q35.2),+r(4)(p16.3q35.2)×2[3]/46,XY,r(4)(p1?q2?)[2]; CMA result was arr[GRCH37]4p16.3(68 345-2 981 614)×1; FISH result was 45,XY,-4[12]/45,XY,-4×2,+mar1.ish r1(4)(WHS-,D4Z1+)[1]/ 46,XY,-4,+mar1.ishr1(4)(WHS-,D4Z1+)[73]/46,XY,-4,+mar2.ishr2(4)(WHS-,D4Z1++)[1]/47,XY,-4,+mar1×2.ishr1(4) (WHS-, D4Z1+)×2[4]/46,XY,del(4)(p16.3).ish del(4)(p16.3)(WHS-,D4Z1+)[9]. CONCLUSION In this case, the ring chromosome 4 as a de novo variant has produced a number of cell lines during embryonic development and given rise to mosaicism. The clinical phenotype of ring chromosome 4 is variable. The instability of the ring chromosome itself, presence of mosaicism, chromosome breakpoint and range of deletion and/or duplication may all affect the ultimate phenotype.
Humans ; Pregnancy ; Female ; Ring Chromosomes ; In Situ Hybridization, Fluorescence ; Karyotyping ; Karyotype ; Mosaicism

OBJECTIVE: To assess the value of copy number variation sequencing (CNV-seq) for the diagnosis of children with disorders of sex development (DSD). METHODS: Five children with DSD who presented at the First Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled. In addition to chromosomal karyotyping, whole exome sequencing (WES), SRY gene testing, and CNV-seq were also carried out. RESULTS: Child 1 and 2 had a social gender of female, whilst their karyotypes were both 46,XY. No pathogenic variant was identified by WES. The results of CNV-seq were 46,XY,+Y (1.4) and 46,XY,-Y (0.75), respectively. The remaining three children have all carried an abnormal chromosome Y. Based on the results of CNV-seq, their karyotypes were respectively verified as 45,X[60]/46,X,del(Y)(q11.221)[40], 45,X,16qh+[76]/46,X,del(Y)(q11.222),16qh+[24], and 45,X[75]/46,XY[25]. CONCLUSION CNV-seq may be used to verify the CNVs on the Y chromosome among children with DSD and identify the abnormal chromosome in those with 45,X/46,XY. Above results have provided a basis for the clinical diagnosis and treatment of such children.
Humans ; Child ; Female ; DNA Copy Number Variations ; Chromosome Aberrations ; Karyotyping ; Exome Sequencing ; Disorders of Sex Development/genetics*

OBJECTIVE: To assess the value of fluorescence in situ hybridization (FISH) technique for the verification of the clonalities of non-clonal cytogenetic abnormalities (n-CCA) identified by conventional chromosome banding analysis (CBA) in patients with Myelodysplastic syndrome (MDS). METHODS: Clinical data and results of karyotyping and FISH assays for 91 patients of MDS with n-CCA identified by CBA were retrospectively analyzed. In total 94 non-clonal +8, 5q-, -7/7q- or 20q- were detected by CBA, among which 43 (45.7%) were verified to be clonal abnormalities by FISH. RESULTS: The detection rates for +8, 5q-, -7/7q- and 20q- by FISH were 47.6% (30/63), 25% (2/8), 41.7% (5/12), 40% (2/5) and 66.7% (4/6), respectively, with the positive cells accounting for 4% to 90% of all counted cells, with a median value of 7%. The 91 patients were divided into three groups including ≥ 20, 10 ~< 20 and < 10 based on the numbers of metaphase cells in CBA, and the detection rates by FISH for the three groups were 43.7% (31/71), 33.3% (3/9) and 63.6% (7/11), respectively, which showed no statistically difference (P > 0.05). Continuous CBA and FISH surveys were conducted for 26 patients who received supportive treatment, and the results revealed that 91.7% (11/12) of FISH-verified positive abnormalities had persisted, whereas 92.9% (13/14) of the n-CCA verified as negative by FISH was transient. CONCLUSION Nearly half of the CBA identified n-CCA have been verified as clonal aberrations by FISH, and the FISH detection rate showed no correlation with the number of metaphase cells. FISH test is strongly recommended for verifying the clonalities of n-CCA detected by CBA, and continuous cytogenetic survey of the patients with MDS is necessary.
Humans ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Chromosome Aberrations ; Karyotyping ; Myelodysplastic Syndromes/genetics*

Karyotype analysis is the basic method in cytogenetics, and is also recognized as the "gold standard" for diagnosing chromosomal disorders. The teaching and training for traditional karyotyping analysis is time-consuming and even boring. The individual's ability for mastering the chromosome morphology can vary greatly. Therefore, it is necessary to improve the teaching method. On the basis of the traditional method, we have added auxiliary analysis software during the teaching. This type of splicing karyotype teaching has increased the students' interest and improved their ability for karyotyping, allowing them to quickly remember the characteristic bands of chromosomes. Through enhanced memory of a large number of karyotypic images, the students' ability to recognize individual chromosomes has improved.
Humans ; Karyotyping ; Karyotype ; Cytogenetics ; RNA Splicing ; Software

OBJECTIVE: To retrospectively analyze sex chromosomal abnormalities and clinical manifestations of children with disorders of sex development (DSD). METHODS: A total of 14 857 children with clinical features of DSD including short stature, cryptorchidism, hypospadia, buried penis and developmental delay were recruited from Zhengzhou Children's Hospital from January 2013 to March 2022. Fluorescence in situ hybridization (FISH) and chromosomal karyotyping were carried out for such children. RESULTS: In total 423 children were found to harbor sex chromosome abnormalities, which has yielded a detection rate of 2.85%. There were 327 cases (77.30%) with Turner syndrome and a 45,X karyotype or its mosaicism. Among these, 325 were females with short stature as the main clinical manifestation, 2 were males with short stature, cryptorchidism and hypospadia as the main manifestations. Sixty-two children (14.66%) had a 47,XXY karyotype or its mosaicism, and showed characteristics of Klinefelter syndrome (KS) including cryptorchidism, buried penis and hypospadia. Nineteen cases (4.49%) had sex chromosome mosaicisms (XO/XY), which included 11 females with short stature, 8 males with hypospadia, and 6 cases with cryptorchidism, buried penis, testicular torsion and hypospadia. The remainder 15 cases (3.55%) included 9 children with a XYY karyotype or mosaicisms, with main clinical manifestations including cryptorchidisms and hypospadia, 4 children with a 47,XXX karyotype and clinical manifestations including short stature and labial adhesion, 1 child with a 46,XX/46,XY karyotype and clinical manifestations including micropenis, hypospadia, syndactyly and polydactyly, and 1 case with XXXX syndrome and clinical manifestations including growth retardation. CONCLUSION Among children with DSD due to sex chromosomal abnormalities, sex chromosome characteristics consistent with Turner syndrome was most common, among which mosaicism (XO/XX) was the commonest. In terms of clinical manifestations, the females mainly featured short stature, while males mainly featured external genital abnormalities. Early diagnosis and treatment are particularly important for improving the quality of life in such children.
Humans ; Male ; Female ; Turner Syndrome/genetics* ; In Situ Hybridization, Fluorescence ; Cryptorchidism ; Hypospadias ; Retrospective Studies ; Quality of Life ; Sex Chromosome Aberrations ; Karyotyping ; Mosaicism ; Disorders of Sex Development/genetics*