Indian Journal of Genetics and Molecular Research

CRISPR-Cas9 is a Nobel Prize winning groundbreaking technology that allows precise editing of an organism’s genome, including that of humans. This technology can specifically modify target DNA sequences, thereby improving its action. The Cas9 enzyme and guide RNA are vital components of the CRISPR-Cas9 complex. The two main mechanisms responsible for its action are non-homologous end joining (NHEJ) and homology-directed recombination (HDR). There are several strategies that can be employed to deliver the CRISPR components into target cells. These include viral vectors, lipofection, electroporation, microinjection, and using nanoparticles. This robust technology has important applications in medicine and agriculture.

Cancer genetics seeks to understand the genetic basis of tumor development through population, cytogenetic, and molecular approaches. It examines inherited mutational occurrences, chromosome abnormalities, and gene-level modifications that are accountable for oncogenesis. Proto-oncogenes, tumor suppressor genes, and DNA repair genes are some of the main molecular elements. Cancer has come to be realized as a genetic disorder by historical events, starting from Hippocrates up to Theodor Boveri. Recent advances single-cell biology, CRISPR, and high-throughput sequencing have transformed diagnostics, prognostics, and individualized treatments. There are difficulties still, though, such as genomic heterogeneity, non-coding mutations, and ethics. The integration of genomic data into clinical management ushers in a new era for precision oncology. New technologies including single-cell biology, CRISPR-Cas9 genome editing, and high-throughput sequencing are changing cancer diagnosis, prognosis, and Finding targeted therapeutic methods in cancer. All these developments notwithstanding, there are still challenges such as intratumoral heterogeneity, non-coding mutations, and use of genomic data ethics. Incorporation of large-scale genomic profiling in clinical oncology is a paradigm-shift period for precision oncology with improved and more personalized treatment of cancer patients.

This case report is directed at genomic testing and genetic counselling in unexplained rare genetic disorders of sudden unexplained death in childhood (SUDC) in a consanguineous couple where all three children, two boys and a girl, died between the ages of 1-4 years. No genetic test had been done previously. Whole exome sequencing (WES) of the parents later, showed that both carried a variant in the Desmoplakin (DSP) gene which has an autosomal recessive pattern of inheritance resulting in cardiomyopathy, and in the Sodium voltagegated channel, beta subunit 3 (SCN3B) gene which has an autosomal dominant inheritance pattern with variable penetrance, late or early onset and is associated with Brugada syndrome. From the case histories, it was possible to determine that the daughter was homozygous for the DSP variant, while the sons inherited the SCN3B variant. During post-test genetic counselling, the reproductive option given was preimplantation genetic testing for monogenic disorders and aneuploidies (PGT-M + PGT-A). This study reasserts the application of genomic testing such as WES in routine medical assisted reproductive practices.