VAMP7 – Rett syndrome

The current evidence linking VAMP7 to Rett syndrome (MONDO_0010726) is limited and derives from candidate gene studies that screened RTT cohorts without identifying definitive pathogenic variants. In a study published in American journal of medical genetics (PMID:10602120), 21 single‐nucleotide polymorphisms in the Xq region were identified, including in VAMP7, but no disease‐causing mutations were reported. A subsequent study in Neuropediatrics (PMID:12075494) evaluated 22 patients with RTT and focused on methylation patterns at X‐linked loci, yet did not demonstrate clear segregation of VAMP7 variants with the phenotype. Thus, despite being included as a candidate gene and assessed in multiple unrelated probands (PMID:12075494), the overall genetic evidence remains modest due to the lack of pathogenic mutations and familial segregation data.

In contrast, functional studies provide moderate support by elucidating mechanisms through which VAMP7 may contribute to disease biology. Research in BMC molecular biology (PMID:21609427) demonstrated that alternative splicing of VAMP7 (also known as SYBL1) generates distinct protein isoforms with variable domain architectures that could impact intracellular vesicle trafficking and neuronal signaling. Additional work in The Journal of biological chemistry (PMID:14672948) detailed the regulation of VAMP7 basal transcription via conserved cis‐elements, underscoring its biological relevance. Although the integration of genetic and functional data does not yet support a definitive diagnostic role for VAMP7 alterations in RTT, the mechanistic insights provided by these studies highlight a potential contributory role that merits further investigation.

References

• American journal of medical genetics • 2000 • Candidate gene analysis in Rett syndrome and the identification of 21 SNPs in Xq PMID:10602120
• Neuropediatrics • 2002 • Altered methylation pattern of the G6 PD promoter in Rett syndrome PMID:12075494
• BMC molecular biology • 2011 • Alternative splicing of the human gene SYBL1 modulates protein domain architecture of Longin VAMP7/TI-VAMP PMID:21609427
• The Journal of biological chemistry • 2004 • Human synaptobrevin-like 1 gene basal transcription is regulated through the interaction of selenocysteine tRNA gene transcription activating factor-zinc finger 143 factors with evolutionary conserved cis-elements PMID:14672948

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