Mutational analysis in different genes underlying severe combined immunodeficiency in seven consanguineous Pakistani families.

BACKGROUND: Severe Combined Immunodeficiency (SCID) is an autosomal recessive inborn error of immunity (IEI) characterized by recurrent chest and gastrointestinal (GI) infections and in some cases associated with life-threatening disorders. METHODOLOGY AND RESULTS: This current study aims to unwind the molecular etiology of SCID and also extended the patients' phenotype associated with identified particular variants. Herein, we present 06 disease-causing variants identified in 07 SCID-patients in three different SCID related genes. Whole Exome Sequencing (WES) followed by Sanger Sequencing was employed to explore genetic variations. The results included identification of two previously reported heterozygous variants in homozygous form for the first time in RAG1gene [(p.Arg410Gln);(p.Arg737His)], followed by a recurrent variant (p.Trp959*) in RAG1, a novel variant in IL2RG (p.Asp48Lfs*24), a recurrent variant in IL2RG (p.Gly271Glu) and a recurrent variant in DCLRE1C (p.Arg191*) gene. CONCLUSION: To conclude, the immune-profiling and WES revealed two novel, two as homozygous state for the first time, and two recurrent disease causing variants contributing valuably to our existing knowledge of SCID.

Techniques to Overcome Difficulty in Device Deliverability to Lesion in Complex PCI.

Percutaneous Coronary Intervention (PCI) has revolutionized the management of Coronary Artery Disease and has become the preferred modality of revascularization in a majority of cases. Nevertheless, situations are encountered frequently where device deliverability to coronary lesions entails technical difficulties due to varied anatomies and lesional complexities like tortuosity, calcifications, length of lesions and vessel morphology. While continuous technological refinements are occurring in PCI hardware armamentarium and stent designs, a number of techniques and their modifications and variations have evolved to increase the applicability of PCI to difficult lesions. The present article envisages a thorough review of all aspects of improving successful device deliverability in complex PCI with prominent emphasis on increasing the backup support of Guide Catheters which is the primary factor of success in difficult coronary lesions.