Relevance to Autism

Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004). Chisholm et al., 2022 analyzed a study cohort of 68 children (3-15 years) with neurofibromatosis type I (NF1) who had scored above threshold on the Social Responsiveness Scale-Second Edition (T-score 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and found that 63% met the ADOS-2 'autism spectrum' cut-off, while 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Large-scale whole-exome and whole-genome seqeuncing studies have identified de novo variants in ASD probands from the Simons Simplex Collection, the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort (Sanders et al., 2012; Iossifov et al., 2014; Zhou et al., 2022). A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified NF1 as a gene reaching exome-wide significance (P < 2.5E-06).

Molecular Function

The encoded protein has Ras GTPase activity and appears to be a negative regulator of cell proliferation.

External Links

References