2021 Highlights

Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases. Ppil4 depletion... 

 A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants...

Congenital hydrocephalus (CH) affects 1 in 1000 births, is a major cause of morbidity, and costs the US health care system $2 billion annually.1 More than 40% of CH cases are thought to have a genetic etiology. However, only less than 5% of CH cases are associated with a defined gene mutation,1 limiting the utility of genetic testing with targeted approaches and underscoring the need for CH gene discovery. The X-linked recessive form of hydrocephalus associated with...