A novel de novo heterozygous multi-exon deletion spanning exons 6-8 of SYT1 was identified in a 13-month-old child with Baker-Gordon syndrome, broadening the mutational spectrum of this disorder and highlighting an alternative pathogenic mechanism beyond missense variants.
Key Findings
Results
A novel de novo heterozygous deletion spanning exons 6-8 of SYT1 was identified as the causative variant in a child with Baker-Gordon syndrome.
The deletion was identified using trio-based whole-exome sequencing with read-depth copy-number variant (CNV) analysis.
The deletion was subsequently confirmed by quantitative PCR.
The variant was confirmed to be de novo (not inherited from either parent) via trio-based analysis.
This represents a multi-exon intragenic deletion affecting key functional domains of SYT1.
Results
The proband presented with a constellation of clinical features consistent with Baker-Gordon syndrome at 13 months of age.
The patient was a 13-month-old Chinese boy.
Clinical features included global developmental delay, axial hypotonia, stereotypic hand-flapping movements, and limited vocalization.
Mild facial dysmorphism was also observed.
Brain MRI revealed a simplified gyral pattern involving the frontal and parietal lobes.
Discussion
Intragenic multi-exon deletions of SYT1 represent an alternative pathogenic mechanism for Baker-Gordon syndrome in addition to the predominantly reported missense variants.
Baker-Gordon syndrome is described as a rare autosomal dominant neurodevelopmental disorder caused by heterozygous pathogenic variants in SYT1.
SYT1 encodes synaptotagmin-1, described as 'a key Ca2+ sensor for synaptic vesicle exocytosis.'
Prior literature had predominantly reported missense variants as the causative mechanism in BGS.
This case broadens the mutational spectrum of BGS to include multi-exon deletions affecting key functional domains.
Conclusions
Exon-level CNV analysis within whole-exome sequencing pipelines has diagnostic value for neurodevelopmental disorders.
The causative deletion in this case was detected via read-depth CNV analysis incorporated into trio-based whole-exome sequencing.
Standard variant calling from exome sequencing may miss intragenic copy-number variants without specific CNV analysis.
The authors highlight 'the value of exon-level CNV analysis in the genetic diagnosis of neurodevelopmental disorders.'
Quantitative PCR was used as a confirmatory method following WES-based CNV detection.
What This Means
This research describes the case of a 13-month-old boy in China who showed signs of a rare brain development disorder called Baker-Gordon syndrome (BGS). His symptoms included delayed development across all areas, weak muscle tone in his core, repetitive hand-flapping movements, difficulty making sounds, and subtle differences in facial features. Brain imaging also showed that the folds in parts of his brain were less complex than typical, a finding called a simplified gyral pattern.
To find the genetic cause, the research team analyzed the DNA of the child and both parents using a technique called whole-exome sequencing, combined with a specialized analysis that can detect missing or duplicated segments of genes (copy-number variant analysis). They found that the child was missing a segment of the SYT1 gene — specifically a stretch covering three sections (exons 6 through 8) — and that this deletion was new (not inherited from either parent). A separate confirmatory lab test verified this finding. The SYT1 gene makes a protein called synaptotagmin-1, which plays a critical role in how brain cells communicate with each other by releasing chemical signals.
This research suggests that BGS can be caused not only by small spelling errors in the SYT1 gene (missense mutations, which were previously the most commonly reported cause) but also by larger deletions that remove whole sections of the gene. This expands the understanding of how BGS can arise. The findings also suggest that including copy-number variant analysis as part of standard genetic testing could help diagnose more children with unexplained neurodevelopmental conditions who might otherwise go undiagnosed.
Xu X, Xu H, Zhang L, He Y. (2026). A novel de novo multi-exon deletion of SYT1 in a child with Baker-Gordon syndrome.. BMC pediatrics. https://doi.org/10.1186/s12887-026-07556-1