RELNReelin

SFARI Gene score

1

High Confidence

Several studies have found a genetic association between the RELN gene and autism. Positive associations have been found in the Italian and US populations (Persico et al., 2001), the Chinese Han population and Caucasian AGRE families. Several studies have also revealed lack of association between RELN and autism in a number of samples, including IMGSAC, CPEA, German and Chinese Han populations. Variable expression data also exists. A de novo LoF variant in the RELN gene was identified in an ASD proband from 2,270 trios screened by the Autism Sequencing Consortium (PMID 25363760), while two de novo likely damaging missense variants have been observed in ASD probands from the Simons Simplex Collection and the Autism Sequencing Consortium (PMID 22542183, 25363760). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) identified RELN as a gene meeting high statistical significance with a 0.01< FDR ?0.05, meaning that this gene had a ?95% chance of being a true autism gene (PMID 25363760). Two additional de novo LoF variants and a likely damaging missense variant in RELN were identified in probands from the Autism Genetic Resource Exchange (AGRE) in Stessman et al., 2017. Lammert et al., 2017 demonstrated that several ASD-associated missense variants in the RELN gene, including a de novo missense variant identified in a Simons Simplex Collection proband, resulted in reduced RELN protein secretion from transfected cells.

criteria met

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

04-01-2017