Fig. 1: DENND5A loss of function variants influence neurodevelopment.

a Schematic of DENND5A protein with all coding sequence variants identified in the study. Red = found in homozygous individuals, blue = found in compound heterozygous individuals. b Venn chart showing the number of people with biallelic DENND5A variants exhibiting the most frequently reported phenotypes and the degree of phenotypic overlap between cohort members. c Funnel chart showing the most common seizure types present in the cohort. d Histogram depicting the number of individuals in a given OFC percentile range. Note that the exact OFC percentile is not known in every case. e Quantification of motor scores from n = 16 individuals with microcephaly and n = 8 individuals without microcephaly. Each dot represents one person. Data are mean ± SEM analyzed via two-tailed Mann-Whitney U test (Z = −2.55, p = 0.011). f Quantification of motor scores from n = 8 individuals with biallelic missense variants, n = 8 individuals with biallelic frameshift or nonsense variants, and n = 8 individuals with an allelic combination of frameshift, nonsense, missense, intronic, or copy number variants in DENND5A. Each dot represents one person. Data are mean ± SEM analyzed via Kruskal-Wallis test followed by pairwise comparisons with Bonferroni corrections for multiple comparisons (H(2) = 7.02, p = 0.03). g Quantification of neurological scores from n = 8 individuals with biallelic missense variants, n = 8 individuals with biallelic frameshift or nonsense variants, and n = 8 individuals with an allelic combination of frameshift, nonsense, missense, intronic, or copy number variants in DENND5A. Each dot represents one person. Data are mean ± SEM analyzed via one-way ANOVA followed by Tukey’s HSD (F(2, 20) = [12.996], p = 0.0002). Source data for each panel are provided as a Source Data file.