ZNF672 and GLUT1 Deficiency Syndrome

In a recent report, a chromosomal rearrangement involving a derivative chromosome 1 in a sibling pair revealed two interstitial deletions, one at 1p34.2 and another at 1q44, with the latter breakpoint mapping to ZNF672 (PMID:20509907). The patients exhibited clinical features including hypotonia, seizure, global developmental delay, facial dysmorphism, hypoglycorrhachia, intellectual disability, ataxia, and microcephaly, which are classically observed in GLUT1 deficiency syndrome. This syndrome is most notably caused by haploinsufficiency of SLC2A1 within the deleted 1p34.2 region, while the contribution of ZNF672 remains unclear.

Genetic evidence linking ZNF672 to GLUT1 deficiency syndrome is limited and derived solely from its involvement in a broader multi‐gene deletion (PMID:20509907). No independent reports of recurrent ZNF672 variants or segregational data in unrelated probands have been published. In the reported sibling pair, only one additional affected relative (the sibling) was identified, and detailed segregation analysis for the 1q44 region was not provided.

Functional studies have consistently demonstrated that disruption of SLC2A1 is responsible for the pathogenic phenotype observed in GLUT1 deficiency syndrome. In contrast, no experimental evidence supports a direct functional role for ZNF672 in the disease mechanism. The absence of in vitro or in vivo assays confirming its involvement further limits the genetic evidence for a definitive association.

Furthermore, the reported deletion in the 1q44 region, where ZNF672 is located, appears to be an incidental finding since the clinical presentation aligns with haploinsufficiency of SLC2A1. Additional case‐series or molecular studies confirming a contributory role for ZNF672 in GLUT1 deficiency syndrome are lacking, leaving its relevance disputed.

In summary, while ZNF672 (HGNC:26179) is incidentally disrupted in a chromosomal deletion that also encompasses the well‐established GLUT1 gene, the current evidence does not support an independent causative association between ZNF672 and GLUT1 deficiency syndrome (MONDO_0000188). Further investigations would be required to determine any contributory role of ZNF672 beyond the established etiology.

Key take‑home: For diagnostic decision‑making, clinicians should prioritize SLC2A1 alterations when evaluating GLUT1 deficiency syndrome, as current evidence does not endorse ZNF672 as a primary disease gene.

References

• Molecular Cytogenetics • 2010 • Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair. PMID:20509907

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