variants in families with complex dystonic syndromes: evidence for phenotypic heterogeneity.

Background: Dystonia involves repetitive movements and muscle contractions leading to abnormal postures. We investigated patients in two families, DYAF11 and M, exhibiting dystonic or involuntary movement disorders.

Methods: Clinical investigations were performed for all patients.

Monogenic variants in dystonia: an exome-wide sequencing study.

Background: Dystonia is a clinically and genetically heterogeneous condition that occurs in isolation (isolated dystonia), in combination with other movement disorders (combined dystonia), or in the context of multisymptomatic phenotypes (isolated or combined dystonia with other neurological involvement). However, our understanding of its aetiology is still incomplete. We aimed to elucidate the monogenic causes for the major clinical categories of dystonia.

A hypomorphic inherited pathogenic variant in DDX3X causes male intellectual disability with additional neurodevelopmental and neurodegenerative features.

Background: Intellectual disability (ID) is a common condition with a population prevalence frequency of 1-3% and an enrichment for males, driven in part by the contribution of mutant alleles on the X-chromosome. Among the more than 500 genes associated with ID, DDX3X represents an outlier in sex specificity. Nearly all reported pathogenic variants of DDX3X are de novo, affect mostly females, and appear to be loss of function variants, consistent with the hypothesis that haploinsufficiency at this locus on the X-chromosome is likely to be lethal in males.