Patient-reported visual function outcomes agree with visual acuity and ophthalmologist-graded scoring of visual function among patients with long-chain 3-hydroxyacylcoA dehydrogenase deficiency (LCHADD).

Patients with LCHADD develop progressive chorioretinopathy with vision loss over time. To date, no data on the impact of vision loss on patient vision-specific activities of daily living or quality of life have been reported. We used validated ophthalmic patient-reported outcome measures (PROMs) to compare the impact of patient-perceived visual function to visual acuity and an ophthalmologist-graded stage of LCHADD chorioretinopathy.

The relationship between baseline BMD and fracture incidence in the placebo groups of RCTs using individual patient data from the FNIH-ASBMR-SABRE Project.

We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip bone mineral density (TH BMD) at two years could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the FNIH-ASBMR-SABRE project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Cancer-associated SF3B1 mutation K700E causes widespread changes in U2/branchpoint recognition without altering splicing.

Myelodysplastic syndromes and other cancers are often associated with mutations in the U2 snRNP protein SF3B1. Common SF3B1 mutations, including K700E, disrupt SF3B1 interaction with the protein SUGP1 and induce aberrant activation of cryptic 3' splice sites (ss), presumably resulting from aberrant U2/branch site (BS) recognition by the mutant spliceosome. Here, we apply the new method of U2 IP-seq to profile BS binding across the transcriptome of K562 leukemia cells carrying the K700E mutation.