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 the gene locus. This approach overlooks causal variants with trans-acting effects on splicing transcriptome-wide, such as variants impacting spliceosome function.

Human organoids for rapid validation of gene variants linked to cochlear malformations.

Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital. The majority of patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for the genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families deafness.

Genome sequencing reveals novel variants in a diverse population with congenital anterior segment anomalies.

Congenital anterior segment anomalies are disorders that affect the development of the eye and cause severe visual impairment. The molecular basis of congenital anterior segment anomalies is not well known. In this study, genome sequencing was performed on 27 families from diverse ethnicities with congenital anterior segment anomalies and 11 variants were identified, most of which were novel and family specific.

Extreme Phenotypic Variability of -Related Disorders in Hearing Loss.

Hearing loss is the most common sensory defect in humans, affecting normal communication. In most cases, hearing loss is a multifactorial disorder caused by both genetic and environmental factors, but single-gene mutations can lead to syndromic or non-syndromic hearing loss. Monoallelic variants in , coding for gamma (γ)-actin, are associated with classical Baraitser-Winter Syndrome type 2 (BRWS2, nonsyndromic deafness, and a variety of clinical presentations not fitting the original BRWS2 description or nonsyndromic deafness.

The effect of disopyramide therapy on functional capacity improvement in patients with obstructive hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular outflow tract obstruction (LVOTO), leading to symptoms and adverse outcomes. Disopyramide, with its negative inotropic effects, is commonly used to reduce LVOTO in obstructive HCM (HOCM). This study evaluates the impact of disopyramide on functional capacity in HOCM patients.