UNASSIGNED: To assess the prevalence and type of chromosomal abnormalities in Brazilian couples with recurrent pregnancy loss (RPL) and compare the clinical characteristics of couples with and without chromosome abnormalities.
UNASSIGNED: We assessed the medical records of 127 couples with a history of two or more miscarriages, referred to a tertiary academic hospital in Belo Horizonte, Brazil, from January 2014 to May 2023. Karyotype was generated from peripheral blood lymphocyte cultures, and cytogenetic analysis was performed according to standard protocols by heat-denatured Giemsa (RHG) banding.
UNASSIGNED: Abnormal karyotypes were detected in 10 couples (7.8%). The prevalence of chromosomal abnormalities was higher among females (6.3%) compared to males (2.0%), but this difference was not statistically significant (p=0.192). The mean number of miscarriages was. 3.3 ± 1.1 in couples with chromosome abnormalities and 3.1 ± 1.5 in couples without chromosome abnormalities (p=0.681). Numerical chromosomal anomalies (6 cases) were more frequent than structural anomalies. Four women presented low-grade Turner mosaicism. No differences were found between couples with and without karyotype alterations, except for maternal age, which was higher in the group with chromosome alterations.
UNASSIGNED: The prevalence of parental chromosomal alterations in our study was higher than in most series described in the literature and was associated with increased maternal age. These findings suggest that karyotyping should be part of the investigation for Brazilian couples with RPL, as identifying the genetic etiology may have implications for subsequent pregnancies.

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 μg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.
目的： 探讨进展期骨髓增生异常综合征（MDS）患儿的临床特征及预后的影响因素。 方法： 回顾性纳入中国医学科学院血液病医院2009年9月至2022年4月诊断为进展期MDS患儿的临床资料，通过电话、查阅病历资料进行随访，随访至2023年5月1日，通过分析染色体核型检测、基因二代测序结果，总结进展期MDS患儿的临床特征；应用多因素Cox回归分析探讨进展期MDS患儿预后的影响因素。 结果： 共纳入69例患儿，男49例，女20例，年龄［M（Q1，Q3）］为8（5，10）岁。67例进行染色体核型检测，42例（62.7%）患儿核型异常，其中7号染色体单体最为常见，有17例（25.4%）；43例行二代测序检查，以SETBP1、NRAS、PTPN11、RUNX1基因突变较为常见，分别有12例（27.9%）、9例（20.9%）、8例（18.6%）、8例（18.6%）。随访时间［M（Q1，Q3）］为26（13，56）个月，5年总生存率为56%（95%CI：44.4%~70.5%）。接受造血干细胞移植（HSCT）患儿的5年总生存率高于未接受HSCT的患儿（73.9%比29.1%，P<0.001）。HSCT（HR=0.118，95%CI：0.037~0.372，P<0.001）是进展期MDS患儿总生存率的保护因素；诊断时铁蛋白水平（>356.3 μg/L）（HR=6.497，95%CI：2.068~20.415，P=0.001）以及脾脏中、重度肿大（HR=4.075，95%CI：1.174~14.141，P=0.027）是进展期MDS患儿总生存率的危险因素。 结论： 进展期MDS患儿最常见的异常染色体核型和突变基因分别是7号染色单体和SETBP1基因。HSCT、铁蛋白增高和脾中、重度肿大是进展期MDS患儿总生存率的影响因素。.

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The prognostic and predictive role of specific gene mutations in Waldenström Macroglobulinemia (WM) is well-ascertained whereas the clinical impact of chromosome aberrations is far less known. Recent work has provided initial evidence for an adverse prognostic impact of some aberrations, such as del(6q), while other studies suggest a possible relationship between some clinical features (e.g. advanced age and/or inflammatory status) and specific cytogenetic abnormalities. To add to the still limited knowledge on WM cytogenetics and its clinical implications, we herein report our experience in a cohort of WM patients across 23 years. Based on our retrospective study, we found that abnormal karyotype was more represented in older patients and maintained a statistically significant independence from other molecular, clinical, and biological features related to WM. The presence and number of cytogenetic aberrations correlated with inferior overall and progression-free survival outcomes regardless of the type of single chromosome aberration. Our data suggests that the role of the altered karyotype deserves to be further clarified especially in elderly WM patients, in whom cytogenetic abnormalities and disease biology appear to be characterized by a higher degree of complexity.

OBJECTIVE: To determine the frequency and characteristics of AZF microdeletions of Y chromosome and karyotypic abnormalities among infertile male patients from southwest China.
METHODS: 4 278 infertile male patients treated at West China Second University Hospital of Sichuan University from September 2018 to July 2023 were selected as the study subjects. Results of Y chromosome microdeletion detection and G-banded karyotyping analysis were retrospectively reviewed.
RESULTS: Clinical data of the patients were collected, which have included 2 048 patients with azoospermia, 1 536 patients with oligozoospermia, 310 patients with mild to moderate oligozoospermia, and 384 patients with infertility but normal sperm concentration. An abnormal karyotype was found in 213 (8.80%) of 2 421 patients who had undergone karyotyping analysis. The frequency of Y chromosome microdeletions was 9.86% (422/4 278), which had occurred in 10.4%, 13.28%, 0.97% and 0.52% of the cases with azoospermia, severe oligozoospermia, mild to moderate oligozoospermia, and infertility with normal sperm concentration, respectively.
CONCLUSIONS: Y chromosome microdeletion detection and karyotyping analysis are crucial for assessing the cause of male infertility. Early diagnosis can facilitate the selection of reproductive methods.

Hemivertebra is a rare congenital abnormality of the spinal column. Hemivertebra with other structural and cytogenetic abnormalities are reported. The prognosis is favorable with partial hemivertebra and with a single spinal defect as compared to a defect involving full segments and affecting different levels of the spines. The perinatal outcome is obscured when it is associated with other syndromes or cytogenetic abnormality. It is imperative to do serial thorough anatomical ultrasound scanning and to screen for chromosomal abnormality when hemivertebra is detected during pregnancy.

BACKGROUND: Retinoblastoma (Rb) is the most common intraocular malignancy in childhood, originating from primitive retinal stem cells or cone precursor cells. It can be triggered by mutations of the RB1 gene or amplification of the MYCN gene. Rb may rarely present with polydactyly.
METHODS: We conducted karyotype analysis, copy number variation sequencing, and whole-genome sequencing on the infant proband and his family. The clinical course and laboratory results of the proband\'s infant were documented and collected. We also reviewed the relevant literature.
RESULTS: A 68-day-old boy presented with preaxial polydactyly and corneal edema. His intraocular pressure (IOP) was 40/19 mmHg, and color Doppler imaging revealed vitreous solid mass-occupying lesions with calcification in the right eye. Ocular CT showed flaky high-density and calcification in the right eye. This was classified as an International Retinoblastoma Staging System group E retinoblastoma with an indication for enucleation. Enucleation and orbital implantation were performed on the child\'s right eye. Karyotype analysis revealed an abnormal 46, XY, 15pstk+ karyotype, and the mother exhibited diploidy of the short arm of chromosome 15. The Alx-4 development factor, 13q deletion syndrome, and the PAPA2 gene have been reported as potential mechanisms for Rb combined with polydactyly.
CONCLUSIONS: We report the case of a baby boy with Rb and polydactyly exhibiting a 46, XY, 15pstk+ Karyotype. We discuss potential genetic factors related to both Rb and polydactyly. Furthermore, there is a need for further exploration into the impact of chromosomal polymorphisms in Rb with polydactyly.

OBJECTIVE: Fetuses with abnormal karyotypes often exhibit distinctive ultrasonographic markers, including major anomalies and \"soft\" markers, indicating potential chromosomal issues. A crucial consideration arises when a single fetal anomaly is detected, raising the question of whether karyotyping is warranted, given the associated procedural risks. Our objective was to establish correlations between single fetal anomalies identified through ultrasound and chromosomal abnormalities.
METHODS: A cross-sectional study analyzed the karyotype of 1493 fetuses and detected a single ultrasonographic anomaly over a 16-year period. Karyotyping was performed using the standard karyotype technique. Moreover, data regarding the type of anomaly detected ultrasonographically, karyotype results, and outcomes following interventions were collected. Among other methods, the use of positive likelihood ratios (LR+) was used to evaluate the diagnostic accuracy of ultrasound compared to karyotyping.
RESULTS: In total, an aberrant karyotype was identified in 99 fetuses (6.6%). This was most commonly observed in cases involving a \"soft\" marker, occurring in 27 out of 218 fetuses (12.4%). The most frequently detected aberrant karyotype resulted from aneuploidies (80.6% of cases), notably trisomy 21 (50.5%). \"Soft\" markers predicted chromosomal issues (LR+ = 1.9; OR = 2.4), and isolated polyhydramnios (LR+ = 1.54; OR = 1.6) showed significance in predicting fetal chromosomal aberrations.
CONCLUSIONS: When assessing the necessity for karyotyping in fetuses with single major anomalies or \"soft\" markers, it is crucial to consider individual risks for chromosomopathies, including the LR+ of the detected marker. In cases where fetuses exhibit isolated anomalies with a normal karyotype, additional diagnostic measures, such as molecular cytogenetic and molecular genetics techniques, may become necessary.

UNASSIGNED: Copy number variations (CNVs) detected by high-resolution single nucleotide polymorphism microarrays (SNP arrays) have been associated with congenital heart defects (CHDs). The genetic mechanism underlying the development of CHDs remains unclear.
UNASSIGNED: High-resolution SNP arrays were used to detect CNVs and traditional chromosomal analyses, respectively, were carried out on 60 and 249 fetuses from gestational 12-37 weeks old, having isolated or complex CHDs that were diagnosed using prenatal ultrasound.
UNASSIGNED: Twenty of the 60 fetuses (33.5%) had abnormalities, of which 23 CNVs (12 pathogenic, five probable pathogenic and six of undetermined significance) were detected by SNP arrays, and two distinct CNVs were present in three of these fetuses. In addition, in 39 patients with isolated congenital heart disease who had normal karyotypes, abnormal CNVs were present in 28.2% (11/39), and in patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs. In patients with complex coronary artery disease, 19.0% (4/21) had abnormal karyotypes and 42.9% (9/21) had abnormal CNVs.
UNASSIGNED: In conclusion, genome-wide high-resolution SNP array can improve the diagnostic rate and uncover additional pathogenic CNVs. The submicroscopic deletions and duplications of Online Mendelian Inheritance in Man (OMIM) genes found in this study have haploinsufficient (deletion) or triplosensitive (duplication) traits, which further clarify the etiology and inheritance of CHDs.

Essential thrombocythemia is a Janus kinase 2 (JAK2) mutation-prevalent myeloproliferative neoplasm characterized by clonal thrombocytosis; clinical course is often indolent but might be interrupted by thrombotic or hemorrhagic complications, microcirculatory symptoms (e.g., headaches, lightheadedness, and acral paresthesias), and, less frequently, by disease transformation into myelofibrosis (MF) or acute myeloid leukemia.
In addition to thrombocytosis (platelets ≥450 × 109 /L), formal diagnosis requires the exclusion of other myeloid neoplasms, including prefibrotic MF, polycythemia vera, chronic myeloid leukemia, and myelodysplastic syndromes with ring sideroblasts and thrombocytosis. Bone marrow morphology typically shows increased number of mature-appearing megakaryocytes distributed in loose clusters.
Approximately 80% of patients express myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL), in a mutually exclusive manner; in addition, about 50% harbor other mutations, the most frequent being TET2 (9%-11%), ASXL1 (7%-20%), DNMT3A (7%), and SF3B1 (5%). Abnormal karyotype is seen in <10% of patients and includes +9/20q-/13q-.
Life expectancy is less than that of the control population. Median survival is approximately 18 years but exceeds >35 years in younger patients. The triple A survival risk model, based on Age, Absolute neutrophil count, and Absolute lymphocyte count, effectively delineates high-, intermediate-1-, intermediate-2-, and low-risk disease with corresponding median survivals of 8, 14, 21, and 47 years.
Four risk categories are considered: very low (age ≤60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (same as low but age >60 years), and high (thrombosis history or age >60 years with JAK2 mutation).
MPL and CALR-1 mutations have been associated with increased risk of MF transformation; spliceosome with inferior overall and MF-free survival; TP53 with leukemic transformation, and JAK2V617F with thrombosis. Leukemic transformation rate at 10 years is <1% but might be higher in JAK2-mutated patients with extreme thrombocytosis and those with abnormal karyotype.
The main goal of therapy is to prevent thrombosis. In this regard, once-daily low-dose aspirin is advised for all patients and twice daily for low-risk disease. Cytoreductive therapy is advised for high-risk and optional for intermediate-risk disease. First-line cytoreductive drugs of choice are hydroxyurea and pegylated interferon-α and second-line busulfan.
The current review includes specific treatment strategies in the context of extreme thrombocytosis, pregnancy, splanchnic vein thrombosis, perioperative care, and post-essential thrombocythemia MF, as well as new investigational drugs.