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GALNT17 is one of several genes encompassed by the typical 7q11.23 deletion observed in Williams syndrome (PMID:12073013, PMID:12088082). This contiguous gene deletion syndrome is characterized by a complex developmental phenotype that has been repeatedly documented in multi‑patient studies. The studies collectively identify cases in which the deletion, including GALNT17, is present in individuals with classical Williams syndrome features.
In one population‐based investigation, three children with Williams syndrome were identified (PMID:12088082), with an additional case observed in a national survey (PMID:12073013). Despite these epidemiologic findings, the contribution of GALNT17 to the overall phenotype is inferred solely from its location within the deletion rather than from discrete, isolated pathogenic variants.
There is currently no report of a single nucleotide or small coding variant in GALNT17—such as a variant described by a complete HGVS coding change (e.g. c.123A>T (p.Lys41Asn))—that is specifically linked to Williams syndrome. This absence of variant‐level evidence confines the genetic data to observations of the gene’s inclusion in the typical deletion, limiting its independent genetic evidence.
Functional studies, however, provide supportive experimental data. In vivo investigations, including a Galnt17 knockout mouse model, have demonstrated that loss‑of‑function leads to developmental delay, abnormal coordination, and cerebellar vermis pathology (PMID:36002036). These findings align with several neurodevelopmental features seen in Williams syndrome and add biological plausibility to GALNT17’s role in neural development.
Overall, while the genetic association of GALNT17 with Williams syndrome remains limited by the lack of variant‐specific evidence, the convergent findings from multiple multi‑patient studies and the supporting functional data suggest that GALNT17 may contribute to the neurodevelopmental aspects of the syndrome. Further research aimed at delineating variant‐level impact could improve diagnostic precision and inform therapeutic strategies.
Key Take‑home Sentence: Although GALNT17’s association with Williams syndrome is currently based on its deletion in affected individuals and corroborated by supportive functional studies, its clinical utility may be enhanced by future studies that clarify its specific contribution to the phenotype.
Gene–Disease AssociationLimitedMultiple multi‑patient studies report Williams syndrome cases with deletions encompassing GALNT17 (PMID:12073013, PMID:12088082), but the absence of discrete point mutations limits the standalone evidential support for this gene. Genetic EvidenceLimitedThe genetic evidence is confined to the regional association, as Williams syndrome cases consistently harbor deletions including GALNT17; however, no independent point mutations or small coding changes have been reported. Functional EvidenceModerateFunctional studies, including a Galnt17 knockout mouse model that recapitulates aspects of neurodevelopmental dysfunction such as cerebellar pathology and behavioral deficits (PMID:36002036), support the gene's contributory role. |