A Novel TPM1 Mutation Causes Familial Hypertrophic Cardiomyopathy in an Indian Family: Genetic and Clinical Correlation.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterised by unexplained left ventricular hypertrophy in the absence of abnormal loading conditions. The global prevalence of HCM is estimated to be 1 in 250 in the general population. It is caused due to mutations in genes coding for sarcomeric proteins. α-tropomyosin (TPM1) is an important protein in the sarcomeric thin filament which regulates sarcomere contraction. Mutations in TPM1 are known to cause hypertrophic cardiomyopathy, dilated cardiomyopathy and left ventricular non-compaction. Mutations in TPM1 causing hypertrophic cardiomyopathy are < 1%. However, some high-risk mutations causing sudden cardiac death are also known in this gene. We present a case of a novel heterozygous TPM1 mutation, NM_001018005.2:c.203A>G, p.Gln68Arg; co-segregating in an Indian family with hypertrophic cardiomyopathy. Our report expands the mutational spectrum of HCM due to TPM1 and provides the correlated cardiac phenotype.

Human breast tumor derived endothelial cells exhibit distinct biological properties.

BACKGROUND INFORMATION: Excessive angiogenesis characterized by leaky, tortuous, and chaotic vasculature is one of the hallmarks of cancers and is significantly correlated to poor prognosis. Disorganized angiogenesis leads to poor perfusion of anti-cancer drugs and limits access to immune cells. Hence, impeding angiogenesis is one of the attractive therapeutic targets to inhibit progression and metastasis in several solid tumors including breast. RESULTS: We have developed a robust and reproducible method for isolating and ex vivo culture of endothelial cells (EC) derived from non-malignant (Endo-N) and malignant (Endo-T) part from clinically characterized human breast tumors. RT-PCR and immunoblotting analysis indicated that these cells exhibited expression of endothelial specific genes such as PECAM-1 (CD31), Endoglin (CD105), eNOS, VE-cadherin, VCAM1, and MCAM. Vasculogenic mimicry and contamination of progenitor EC recruited in tumors was ruled out by absence of CD133 expression and normal karyotype. Both the cell types showed stable expression of CD31 and CD105 up to seven passages. Furthermore, compared to Endo-N cells, Endo-T cells showed (a) constitutively increased proliferation marked by nearly 36% of cells in mitotic phase, (b) requirement of glutamine for cell survival, (c) pro-migratory phenotype, (d) produced increased number of sprouts in 3D cultures, and (e) resistance to sorafenib. CONCLUSION: Tumor derived EC showed distinct biological properties compared to normal breast EC. SIGNIFICANCE: Our method for isolating endothelial cell types from human breast tumors may be explored to (a) understand cellular and molecular mechanisms, (b) screen anti-angiogenic molecules, and (c) formulate organoid cultures to develop personalized medicine facilitating better clinical management of breast cancers.

Gerbode Ventricular Septal Defect -A Rare Cardiac Anomaly Associated with Genetic Variants in Indian Population- A Case Series.

Gerbode defects are rare Ventricular Septal Defects (VSD) constituting approximately one percent cases of congenital heart diseases. The genetic predispositions towards the Gerbode Defect (GD) have remained an unexplored area of study till date. We investigated the genotype-phenotype correlation in patients with Gerbode VSD. Molecular genetic study on Sanger sequencing and subsequent data analysis showed that the contributing sequence variations in the NKX2-5, GATA4 and TBX5 gene lies in one of the highly conserved regions and this region is responsible for encoding a functional protein. The resulting genotype variation may be responsible for causing the diseased phenotype known as GD.

Cytogenetic evaluation of patients with clinical spectrum of Turner syndrome.

AIM: The objective of this study was to correlate the genotype, of female patients, withshort stature and primary amenorrhea. MATERIALS AND METHODS: One hundred and forty-six subjects were recruited during 2005-2012. Microscopic and automated karyotyping analyses were done by using chromosomes isolated from the lymphocytes using Giemsa banding (GTG) to identify chromosome abnormalities. RESULTS: A total of 146 clinically suspected Turner syndrome (TS) subjects were recruited for the study, of which, 61 patients were identified to have chromosome abnormalities. The chromosomal abnormalities detected were as follows: Monosomy X (n = 19, 13.01%), triple X syndrome (n = 4, 2.7%), mosaic TS (n = 12, 8.21%), XY gonadal dysgenesis (n = 13, 8.9%), and structural abnormalities including X chromosome (n = 15, 10.27%) and one patient each with autosomal changes involving 9qh inversion and translocation of chromosomes 12 and 14. CONCLUSION: Karyotype abnormalities accounting for 46% in this study emphasize the need for karyotype testing in cases of short stature with primary amenorrhea.