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

Recently, a novel African ancestry specific Parkinson's disease (PD) risk signal was identified at the gene encoding glucocerebrosidase ( ). 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.

Parkinson's Disease Pathogenic Variants: Cross-Ancestry Analysis and Microarray Data Validation.

Background: Known pathogenic variants in Parkinson's disease (PD) contribute to disease development but have yet to be fully explored by arrays at scale.

Objectives: This study evaluated genotyping success of the NeuroBooster array (NBA) and determined the frequencies of pathogenic variants across ancestries.

Method: We analyzed the presence and allele frequency of 34 pathogenic variants in 28,710 PD cases, 9,614 other neurodegenerative disorder cases, and 15,821 controls across 11 ancestries within the Global Parkinson's Genetics Program dataset.

International workshop: what is needed to ensure outcome measures for Rett syndrome are fit-for-purpose for clinical trials? June 7, 2023, Nashville, USA.

Introduction: The clinical, research and advocacy communities for Rett syndrome are striving to achieve clinical trial readiness, including having fit-for-purpose clinical outcome assessments. This study aimed to (1) describe psychometric properties of clinical outcome assessment for Rett syndrome and (2) identify what is needed to ensure that fit-for-purpose clinical outcome assessments are available for clinical trials.

Methods: Clinical outcome assessments for the top 10 priority domains identified in the Voice of the Patient Report for Rett syndrome were compiled and available psychometric data were extracted.

Measuring the Burden of Epilepsy Hospitalizations in CDKL5 Deficiency Disorder.

Background: Information on the hospital service use among individuals with CDKL5 Deficiency Disorder, an ultrarare developmental epileptic encephalopathy, is limited, evidence of which could assist with service planning. Therefore, using baseline and longitudinal data on 379 genetically verified individuals in the International CDKL5 Disorder Database, we aimed to investigate rates of seizure-related and other hospitalizations and associated length of stay in this cohort.

Methods: Outcome variables were lifetime count of family-reported hospitalizations and average length of stay both for seizure- (management and/or investigative) and non-seizure-related causes.

Hospitalizations Following Complex Hip Surgery in Children with Intellectual Disability: A Self-Controlled Case Series Analysis.

Objective: To evaluate the associations between complex hip surgery and subsequent hospitalizations in children with intellectual disability, including a subset of children with cerebral palsy.

Study Design: We conducted a retrospective cohort study using linked administrative, health, and disability data from Western Australia. Children born between 1983 and 2009 who underwent complex hip surgery by end 2014 were included (intellectual disability, n = 154; subset with cerebral palsy, n = 91).