Transcriptome-wide outlier approach identifies individuals with minor spliceopathies.

RNA-sequencing has improved the diagnostic yield of individuals with rare diseases. Current analyses predominantly focus on identifying outliers in single genes that can be attributed to cis-acting variants within or near that gene. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function.

Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease.

Congenital anomalies (CA) affect 3-5% of newborns, representing the second-leading cause of infant mortality in Argentina. Multiple congenital anomalies (MCA) have a prevalence of 2.26/1000 births in newborns, while congenital heart diseases (CHD) are the most frequent CA with a prevalence of 4.

Oculocutaneous albinism type 1B associated with a functionally significant tyrosinase gene polymorphism detected with Whole Exome Sequencing.

: Oculocutaneous albinism (OCA) is a Mendelian disorder characterized by hypopigmentation of the skin, hair, and eyes, hypoplastic fovea, and low vision, known to be caused by mutations in the Tyrosinase (TYR) gene. Among the known TYR variants, some reduce but do not completely eliminate tyrosinase activity, allowing residual production of melanin and resulting in a contradictory assignment as either pathogenic or benign, preventing a precise clinical diagnostic.: In the present work, we performed Whole Exome Sequencing and subsequent Sanger sequencing in a young male clinically diagnosed with OCA.