BACKGROUND Advances in next generation sequencing technologies have revolutionized our ability to discover the causes of rare genetic diseases. However, developing treatments for these diseases remains challenging. In fact, when we systematically analyze the US FDA orphan drug list, we find that only 8% of rare diseases have an FDA-designated drug. Our approach leverages three primary insights:...

BACKGROUND Though rare in occurrence, patients with rare bleeding disorders (RBDs) are highly heterogeneous and may manifest with severe bleeding diathesis. Due to the high rate of consanguinity in many caste groups, these autosomal recessive bleeding disorders which are of rare occurrence in populations across the world, may not be as rare in India. OBJECTIVES To comprehensively analyze the ...

In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain muta...

Hydatidiform moles are the most common type of gestational trophoblastic neoplasia. Hyperproliferative vesicular trophoblasts and imperfect fetal development abnormal pregnancies, recurrent hydatidiform rare. Mutations in NLRP7 responsible for mole. Genetic heterogeneity has been demonstrated patients with mutation. This study presents our case gravida 11, parity 0, histopathologically diagnose...

Strong evidence suggests that rare mutations of severe effect are responsible for a substantial portion of complex human disease. Evolutionary forces generate vast genetic heterogeneity in human illness by introducing many new variants in each generation. Current sequencing technologies offer the possibility of finding rare disease-causing mutations and the genes that harbor them.

1 Rare stochastic mutations may accumulate during dormancy of stem-like cells, but technical 2 limitations in DNA sequencing have limited exploring this possibility. In this study, we 3 employed a recently established deep sequencing method termed Duplex Sequencing to conduct 4 a genome-wide analysis of mitochondrial (mt) DNA mutations in a human breast stem cell 5 model that recapitulates the ...

Background: elexacaftor/tezacaftor/ivacaftor (ETI) is approved for CF patients with at least one F508del mutation. The concept of “Theratyping”—aligning genotypes based on their in vitro response to CFTR modulators, enabled approval ETI rarer mutations. We report a rare mutation that was responsive both and vivo. Mutation description: Q1100P an ultra-rare mutation, carried by seven Israeli Arab...

Nowadays, EGFR TKIs (epidermal growth factor receptor-tyrosine kinase inhibitors) targeted therapy is well established treatment for patients with the so-called EGFR common mutations with advanced or metastatic nonsmall cell lung cancer. The efficacy for the so-called rare and especially for the very rare complex EGFR mutations is not clear. We describe a case of a 63- year-old female with meta...

chédiak-higashi syndrome is a rare autosomal recessive congenital immunodeficiency mainly characterized by a condition called oculo-cutaneous albinism. the affected subjects have light-colored hair, vision problems, blood clotting (coagulation) abnormalities and in adulthood varying neurologic disorders. recurrent infections, particularly viral infection with other disorders in childhood are us...