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Introduction: Myelodysplastic syndrome (MDS) is a heterogeneous disease characterized by cytopenia, marrow dysplasia and has a propensity to develop into acute myeloid leukemia. The disease progression is majorly affected by genetic defects. However, about 40–50% of patients with MDS present with a normal karyotype and develop different courses of disease. Hence, there remains a room to advance the biological understanding and find molecular prognostic markers for cytogenetically normal MDS. Methods: We performed a high-resolution CGH + SNP array along with next-generation sequencing (NGS) of 77 primary diagnosed MDS patients, and also they were clinically followed up. Results: Our study revealed 82 clinically significant genomic lesions (losses/gains) in 49% of MDS patients. CGH + SNP array reduced the proportion of normal karyotype by 30%. SNP array in combination with NGS confirmed the biallelic loss of function of the TP53 gene (2/6), which is a clinically relevant biomarker and new genetic-based MDS entity, i.e., MDS-biTP53, as per the new WHO classification 2022. Genomic region 2p22.3 presented with frequent lesions and also with a more hazard ratio (2.7, 95% CI: 0.37–21) when analyzed by Kaplan-Meier survival analysis. Conclusion: CGH + SNP array changed the cytogenetic and IPSS-R risk group in 18% and 13% of patients, respectively, with an improved prediction of prognosis. This study emphasizes the cytogenetic heterogeneity of MDS and highlights that abnormality with chromosome 2 may have a diagnostic and prognostic impact. Highlights: The study identified 82 different clinically significant CNVs including chromosomal aberrations in MDS. The transcriptome data revealed that CNVs majorly affect genes associated with biological functions such as transcriptions, cell cycle, and immunity. A high frequency of CNVs/loss of heterozygosity was identified at 2p22.3 chromosomal region and found to be associated with disease prognosis. Combination of SNP array with gene mutations successfully established a new genetic-based MDS entity, i.e., MDS-biTP53, in 33.3% of TP53-mutated patients. [ABSTRACT FROM AUTHOR]

Context: Chromosomal abnormalities play an important role in diagnosis and prognosis of hematological diseases. Aims: The aim of the present study was to study the pattern and frequency of chromosomal aberrations in acute myeloid leukemia (AML) subgroups from western India. Settings and Design: A retrospective study was conducted through evaluating laboratory proforma which were filled during 2005 to 2014 for diagnosis and treatment of AML subjects. Methods and Material: We have studied chromosomal aberrations in 282 subjects with AML from western India. AML patients were sub‑grouped according to FAB classification. Cytogenetic study using conventional cytogenetics (GTG‑banding) and Fluorescence in situ hybridization (FISH) was carried out using FISH probes (AML1/ETO, PML/RARA, CBFB). Statistical analysis: Student’s t test for continuous variables and Pearson’s Chi‑squared test for categorical variables were used to identify the relationship between variables. Results: Cytomorphological study revealed AML‑ M3 as most frequent (32.3%) group followed by AML‑M2 (25.2%) and AML‑M4 (19.9%). Chromosomal abnormalities were identified in 145 (51.42%) of the total AML cases. A high frequency (38.6%) of chromosomal abnormalities was identified in AML‑M3 subgroup as compared to AML‑M2 (31%) and AML‑M4 (20.6%). Conclusions: Cytogenetic study is important for the diagnosis and management of the AML patients. Our study identified chromosomal abnormalities in AML subgroups with varied frequencies. It is important in diagnosis and monitoring of the disease. As younger AML patients were more affected in our study, etiological factors such as environmental factors need to be studied. Combination of conventional cytogenetics and FISH has an advantage of identifying high frequency of chromosomal aberrations in AML patients. [ABSTRACT FROM AUTHOR]

Dyskeratosis congenita (DC) is an inherited, progressive bone marrow failure (BMF) and cancer predisposition syndrome with a prevalence of one in 1,000,000 people. In this report, we present a case of a young male patient harboring a novel mutation in the I DKC1 i gene and manifesting the classical clinical triad of DC and BMF. Dyskeratosis congenita is an inherited multisystem bone marrow failure syndrome associated with very high risk of developing aplastic anemia, MDS, leukemia, and solid tumors. In summary, the novel variant identified herein, the DKC1 gene, provides scientific evidence for the genotype-phenotype correlation of DC and has important implications for the clinical and molecular characterization of the disease. [Extracted from the article]

Byline: Babu Rao. Vundinti, Lily. Kerketta, Seema. Korgaonkar, Kanjaksha. Ghosh We describe a five-year-old proband presented with Dandy-Walker malformations, right microopthalmia, hamstring contractures, undescended testis with absence of testis in [...]

Objectives: The aim of this study was to estimate the frequency of chromosomal abnormalities and establish the association with clinical of factors such as secondary sexual characters and gonad development in primary amenorrhea (PA). Study Design: The study was carried out in a large cohort of PA. The chromosomal aberrations were correlated with secondary sexual characters and anatomical abnormalities. Materials and Methods: The data of 490 cases of PA were collected retrospectively. The chromosomal preparations were done from the peripheral blood and subjected to giemsa-trypsin-giemsa banding and karyotyped according to the International System of Human Cytogenetic Nomenclature 2013. The fluorescence in situ hybridization was carried out using centromeric and whole painting probes for X and Y chromosome. Statistical Analysis: Statistical analysis of the data was performed using online version of social science statistics software. Results: A high frequency of abnormal uterus (81.9%) and ovaries (86.7%) were detected in our study. A total of 121 (24.7%) cases were identified with abnormal karyotype. The numerical chromosomal abnormalities were identified in 53 (43.8%) cases while structural abnormalities were identified in 32 (26.4%) cases. The XY karyotype was detected in 29.8% females with PA. The PA individuals with anatomical abnormalities (84.3%) had a high frequency (24.6%) of chromosomal aberrations. Conclusions: The present study concluded that cytogenetics plays an important role in precise diagnosis which helps in the management of PA. The cytogenetic analysis should be carried out to know the genetic basis of PA. [ABSTRACT FROM AUTHOR]