A De novo Loss-of-Function Mutation in PAFAH1B1 Identified in a Single Case with Agyria-Pachygyria Complex

To identify genetic causes in affected infants with abnormalities of brain development, including malformations of cortical development-associated neuropsychological disorders, affected infants were recruited based on their clinical examination and cranial imaging studies. Trio whole-exome sequencing (WES), bioinformatic analysis, and genotype-phenotype correlations were performed for 20 affected subjects to identify candidate mutations, followed by Sanger sequencing for further verification. In the present study, we identified a de novo heterozygous mutation (c.265C > T, p.R89*) of the PAFAH1B1 gene in the affected child with epilepsy, speech impairment, and cerebral palsy. The mutation was predicted to be a null loss-of-function allele, which was not found in ExAC and the Chinse Han Exome Sequences databases. Magnetic resonance imaging of the brain demonstrated bilateral parieto-occipital and temporal lissencephaly as well as frontal partial pachygyria in the affected child. This is the first case with agyria-pachygyria complex due to a nonsense mutation in the Chinese population identified by a trio WES approach.