PASK – 2q37 Microdeletion Syndrome

In a reported case of 2q37 microdeletion syndrome, the candidate gene PASK (HGNC:17270) was found to be markedly downregulated in a patient with autism and brachymetaphalangy (PMID:19365831). The study employed molecular cytogenetic methods including array-based comparative genomic hybridization and fluorescence in situ hybridization to define a 3.5 Mb de novo deletion at 2q37.3. Downregulation of PASK, alongside FARP2 and HDLBP, was detected by expression analyses in patient-derived lymphoblastoid cell lines, suggesting that haploinsufficiency of these genes may contribute to the clinical phenotype. Although the observed expression change provides a potential mechanistic link to the syndrome, the evidence is based on a single proband and lacks corroborative variant-level or segregation data from unrelated families. This single-case genetic finding limits the strength of the association, yet it offers an important perspective for gene prioritization in this chromosomal disorder. Furthermore, while additional studies have explored PASK’s role in other disease contexts, they do not extend the evidence for 2q37 microdeletion syndrome beyond the initial report.

The available genetic and expression data, while nuanced, support a tentative role for PASK in the pathogenesis of 2q37 microdeletion syndrome. However, further cases and functional validations are essential to solidify this association for routine clinical diagnostic decision-making and commercial assay development. Key take‑home: even limited evidence from robust cytogenetic and expression studies may direct future research and enhance the clinical utility of candidate gene evaluation in complex deletion syndromes.

References

• American journal of medical genetics. Part A • 2009 • FARP2, HDLBP and PASK are downregulated in a patient with autism and 2q37.3 deletion syndrome PMID:19365831

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