Autism spectrum disorder (ASD) and schizophrenia (SCZ) are two common neurodevelopmental syndromes that result from the combined effects of environmental and genetic factors. We set out to test the hypothesis that rare variants in many different genes, including de novo variants, could predispose to these conditions in a fraction of cases. In addition, for both disorders, males are either more significantly or more severely affected than females, which may be explained in part by X-linked genetic factors. Therefore, we directly sequenced 111 X-linked synaptic genes in individuals with ASD (n=142; 122 males and 20 females) or SCZ (n=143; 95 males and 48 females). We identified >200 non-synonymous variants, with an excess of rare damaging variants, which suggest the presence of disease-causing mutations. Truncating mutations in genes encoding the calcium-related protein IL1RAPL1 (already described in Piton et al. Hum Mol Genet 2008) and the monoamine degradation enzyme monoamine oxidase B were found in ASD and SCZ, respectively. Moreover, several promising non-synonymous rare variants were identified in genes encoding proteins involved in regulation of neurite outgrowth and other various synaptic functions (MECP2, TM4SF2/TSPAN7, PPP1R3F, PSMD10, MCF2, SLITRK2, GPRASP2, and OPHN1).

Restless legs syndrome (RLS) is a common sensorimotor disorder1 where familial aggregation strongly suggests an important genetic component. However, the underlying genetic structure remains largely unknown. Due to its recent acceptance as a clinical entity and the development of standard diagnostic criteria and reliable assessment instruments,1 few and incomplete RLS twin studies have been published.2,3 ### Methods. A validated 36-item RLS questionnaire, used for our family studies of RLS4 and reformatted to be self-administered, and a standard zygosity questionnaire were individually mailed to 600 adult co-twins (age 18 years and older) from the University of British Columbia (UBC) twin registry across Canada.5 An additional 86 co-twins were identified through our family studies in Quebec (Universite de Montreal [UdeM]) and were telephone interviewed by a trained research associate using the same questionnaires. The pairs with mean zygosity scores of ≥4 were classified as monozygotic (MZ) and all others as dizygotic (DZ).6 Only individuals fulfilling all four diagnostic criteria1 were classified as definite RLS; individuals missing one essential diagnostic criterion but having one or more supporting …

The authors investigated genetic factors contributing to restless legs syndrome (RLS) by performing a 10-cM genome-wide scan in a large French-Canadian pedigree. They detected an autosomal-dominant locus mapping to chromosome 20p13, with a maximum multipoint lod score of 3.86 at marker D20S849. This is the third reported autosomal-dominant locus for RLS and the first autosomal-dominant RLS locus in the French-Canadian population.

A new restless legs syndrome locus on chromosome 14 recently has been reported in one family of Italian origin. Our study aimed to replicate this finding and determine the importance of this locus in the French Canadian population. Markers spanning the region were genotyped in 14 large families and linkage assessed using two-point and multipoint logarithm of odds scores. Possible linkage to this locus was found in one of our kindreds providing support for the existence of this locus and indicating that this locus may be responsible for a small fraction of French Canadian restless legs syndrome.