CD300LF – Autism Spectrum Disorder

In a recent study investigating the genetic underpinnings of autism spectrum disorder, a rare heterozygous truncating variation in CD300LF was identified in a multiplex family. The study employed whole‐exome sequencing in a family with four affected individuals, suggesting that rare loss‐of‐function alleles in CD300LF could be risk candidates for autism spectrum disorder (PMID:25601189).

Genetic evidence stems from the detection of a truncating variant that segregated with disease among affected family members. In this family, one proband and three additional affected relatives carried the candidate variant, supporting a tentative causal role, although the signal did not replicate in a follow‑up cohort of 243 patients and 667 controls (PMID:25601189).

The mode of inheritance appears to be autosomal dominant, as the heterozygous state of the truncating variant was observed in affected individuals of a multiplex family. Segregation analysis, albeit limited to this single pedigree, provided moderate support with three additional affected relatives showing concordant segregation.

A representative variant reported is formatted as follows: c.783del (p.Pro261fsTer266). This frameshift variant likely results in premature protein truncation and loss of normal function, a finding that is consistent with the proposed haploinsufficiency mechanism in neurodevelopmental disorders.

Despite the intriguing findings in the family, the lack of replication in a broader case‑control study and limited functional assessment in the context of autism spectrum disorder restrict the strength of the genetic evidence. Moreover, while independent studies have described functional consequences for related CD300 family members in multiple sclerosis, no direct experimental studies have yet validated the impact of CD300LF truncation on autism‑related phenotypes.

Overall, the association between CD300LF and autism spectrum disorder is currently best classified as Limited. Additional large‐scale genetic studies and functional experiments specifically addressing the role of CD300LF in neurodevelopment are needed. Key take‑home message: Although a rare truncating variant in CD300LF appears to segregate with autism in a multiplex family, caution is warranted in clinical interpretation until further replication and mechanistic data are available.

References

• Psychiatry and clinical neurosciences • 2015 • Rare heterozygous truncating variations and risk of autism spectrum disorder: Whole‑exome sequencing of a multiplex family and follow‑up study in a Japanese population PMID:25601189

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