Parkinson's disease is characterized by resting tremor, rigidity, and bradykinesia caused by the loss of dopaminergic neurons in the substantia nigra, a good response to levodopa, and the presence of Lewy bodies. The recently identified G2019S mutation in exon 41 of the leucine-rich repeat kinase 2 gene (LRRK2) accounts for 2 to 6 percent of familial and 1 to 2 percent of sporadic cases.¹ The mutation is less common in Asian populations¹ but prevalent in patients from North Africa who have Parkinson's disease, as we describe here.

The spliceosome, a ribonucleoprotein complex that includes proteins and small nuclear RNAs (snRNAs), catalyzes RNA splicing through intron excision and exon ligation to produce mature messenger RNAs, which, in turn serve as templates for protein translation. We identified four point mutations in the U4atac snRNA component of the minor spliceosome in patients with brain and bone malformations and unexplained postnatal death [microcephalic osteodysplastic primordial dwarfism type 1 (MOPD 1) or Taybi-Linder syndrome (TALS); Mendelian Inheritance in Man ID no. 210710]. Expression of a subgroup of genes, possibly linked to the disease phenotype, and minor intron splicing were affected in cell lines derived from TALS patients. Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival.

To assess the worldwide variation of amyotrophic lateral sclerosis (ALS) incidence, we performed a systematic review and meta-analysis of population-based data published to date. We reviewed Medline and Embase up to June 2015 and included all population-based studies of newly diagnosed ALS cases, using multiple sources for case ascertainment. ALS crude and standardized incidence (on age and sex using the US 2010 population) were calculated. Random effect meta-analysis and meta-regression were performed using the subcontinent as the main study level covariate. Sources of heterogeneity related to the characteristics of the study population and the study methodology were investigated. Among 3216 records, 44 studies were selected, covering 45 geographical areas in 11 sub-continents. A total of 13 146 ALS cases and 825 million person-years of follow-up (PYFU) were co-nsidered. The overall pooled worldwide crude ALS incidence was at 1.75 (1.55–1.96)/100 000 PYFU; 1.68 (1.50–1.85)/100 000 PYFU after standardization. Heterogeneity was identified in ALS standardized incidence between North Europe [1.89 (1.46–2.32)/100 000 PYFU] and East Asia [0.83 (0.42–1.24)/100 000 PYFU, China and Japan P = 0.001] or South Asia [0.73 (0.58–0.89)/100 000/PYFU Iran, P = 0.02]. Conversely, homogeneous rates have been reported in populations from Europe, North America and New Zealand [pooled ALS standardized incidence of 1.81 (1.66-1.97)/100 000 PYFU for those areas]. This review confirms a heterogeneous distribution worldwide of ALS, and sets the scene to sustain a collaborative study involving a wide international consortium to investigate the link between ancestry, environment and ALS incidence.