YME1L1 and Autism Spectrum Disorder

Two independent multi‐patient studies have identified de novo variants in YME1L1 from autism spectrum disorder (ASD) cohorts, supporting a potential albeit preliminary association with ASD (PMID:37961520, PMID:38519481). In one study, a de novo variant, c.1981G>A (p.Glu661Lys), was reported in an ASD proband. The overall genetic evidence is limited by the low number of independent probands and the absence of segregation data, with the inheritance pattern consistent with autosomal dominant effects observed in de novo mutations.

The genetic evidence is anchored by the identification of a specific coding variant, though functional studies directly linking YME1L1 dysfunction to ASD are currently lacking. While YME1L1 is known to play an essential role in mitochondrial quality control and dynamics—as demonstrated in functional assessments of mitochondrial processing and fusion—the experimental data have not been directly extended to ASD pathophysiology. Key take‑home message: Although initial genetic findings implicate YME1L1 in ASD risk, further segregation analyses and targeted functional studies are imperative to substantiate its clinical utility in diagnostic decision‑making and future research.

References

• Unknown Journal | Unknown Year | Multi‐patient study implicating de novo variants in ASD PMID:37961520
• Unknown Journal | Unknown Year | Expanded analysis of de novo variants in ASD candidate genes PMID:38519481
• The Journal of Cell Biology | 2007 | OPA1 processing controls mitochondrial fusion and is regulated by mRNA splicing, membrane potential, and Yme1L PMID:17709429
• Biology of the Cell | 2008 | Metalloprotease‑mediated OPA1 processing is modulated by the mitochondrial membrane potential PMID:18076378

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