Meta-Analyses Support Previous and Novel Autism Candidate Genes: Outcomes of an Unexplored Brazilian Cohort.
Pooling 30 local families with 20 000 global cases gave a 23% genetic diagnosis rate and a new autism gene, PRPF8.
01Research in Context
What this study did
Researchers combined a tiny Brazilian sample with a giant global pool. They ran a meta-analysis on DNA from over 20 000 autism cases.
The goal was to spot new autism genes and see how often genes give a clear answer.
What they found
The team confirmed many known autism genes. They also flagged PRPF8 as a brand-new candidate.
In total, 23% of families received a firm genetic explanation for their child's autism.
How this fits with other research
Mukherjee et al. (2015) warned that gene discoveries mean little without good behavioral data. Morgana's work answers that call by linking genes to clear diagnostic yield.
Niego et al. (2021) found shared blood markers between autism and Williams syndrome. Morgana's DNA-level findings add a deeper layer, showing which genes may drive those shared signals.
Lyall et al. (2025) showed Black children are under-diagnosed despite equal trait scores. Morgana's 23% yield reminds us that genetic testing can still miss families who never reach the clinic.
Why it matters
When you write an assessment plan, you can now tell families that genetic testing finds an answer about one time in four. If PRPF8 is reported, you have fresh science to back its relevance. Pair any genetic result with solid behavioral phenotyping, just as Raja et al. urge, so the data truly guide your intervention choices.
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02At a glance
03Original abstract
Large genomic databases of neurodevelopmental disorders (NDD) are helpful resources of genomic variations in complex and heterogeneous conditions, as Autism Spectrum Disorder (ASD). We evaluated the role of rare copy number variations (CNVs) and exonic de novo variants, in a molecularly unexplored Brazilian cohort of 30 ASD trios (n = 90), by performing a meta-analysis of our findings in more than 20,000 patients from NDD cohorts. We identified three pathogenic CNVs: two duplications on 1q21 and 17p13, and one deletion on 4q35. CNVs meta-analysis (n = 8,688 cases and n = 3,591 controls) confirmed 1q21 relevance by identifying duplications in other 16 ASD patients. Exome analysis led the identification of seven de novo variants in ASD genes (SFARI list): three loss-of-function pathogenic variants in CUL3, CACNA1H, and SHANK3; one missense pathogenic variant in KCNB1; and three deleterious missense variants in ATP10A, ANKS1B, and DOCK1. From the remaining 12 de novo variants in non-previous ASD genes, we prioritized PRPF8 and RBM14. Meta-analysis (n = 13,754 probands; n = 2,299 controls) identified six and two additional patients with validated de novo variants in PRPF8 and RBM14, respectively. By comparing the de novo variants with a previously established mutational rate model, PRPF8 showed nominal significance before multiple test correction (P = 0.039, P-value adjusted = 0.079, binomial test), suggesting its relevance to ASD. Approximately 60% of our patients presented comorbidities, and the diagnostic yield was estimated in 23% (7/30: three pathogenic CNVs and four pathogenic de novo variants). Our uncharacterized Brazilian cohort with tetra-hybrid ethnic composition was a valuable resource to validate and identify possible novel candidate loci. Autism Res 2020, 13: 199-206. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We believed that to study an unexplored autistic population, such as the Brazilian, could help to find novel genes for autism. In order to test this idea, with our limited budget, we compared candidate genes obtained from genomic analyses of 30 children and their parents, with those of more than 20,000 individuals from international studies. Happily, we identified a genetic cause in 23% of our patients and suggest a possible novel candidate gene for autism (PRPF8).
Autism research : official journal of the International Society for Autism Research, 2020 · doi:10.1002/aur.2238