Toward 3D facial analysis for recognizing Mendelian causes of autism spectrum disorder.

Recognizing Mendelian causes is crucial in molecular diagnostics and counseling for patients with autism spectrum disorder (ASD). We explored facial dysmorphism and facial asymmetry in relation to genetic causes in ASD patients and studied the potential of objective facial phenotyping in discriminating between Mendelian and multifactorial ASD. In a cohort of 152 ASD patients, 3D facial images were used to calculate three metrics: a computational dysmorphism score, a computational asymmetry score, and an expert dysmorphism score.

De novo missense variants in the E3 ubiquitin ligase adaptor KLHL20 cause a developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder.

Purpose: KLHL20 is part of a CUL3-RING E3 ubiquitin ligase involved in protein ubiquitination. KLHL20 functions as the substrate adaptor that recognizes substrates and mediates the transfer of ubiquitin to the substrates. Although KLHL20 regulates neurite outgrowth and synaptic development in animal models, a role in human neurodevelopment has not yet been described.

Shared heritability of human face and brain shape.

Evidence from model organisms and clinical genetics suggests coordination between the developing brain and face, but the role of this link in common genetic variation remains unknown. We performed a multivariate genome-wide association study of cortical surface morphology in 19,644 individuals of European ancestry, identifying 472 genomic loci influencing brain shape, of which 76 are also linked to face shape. Shared loci include transcription factors involved in craniofacial development, as well as members of signaling pathways implicated in brain-face cross-talk.

Author Correction: Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.

Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC.