Whole-Genome Sequencing Identifies a Novel Deep Intronic ADAMTS17 Variant in Weill–Marchesani Syndrome 4

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Background: Weill-Marchesani syndrome 4 (WMS4) is a rare autosomal recessive disorder caused by ADAMTS17 variants, yet deep intronic variants and their splicing-disruptive effects remain poorly explored, limiting diagnostic yields. Results: Whole-genome sequencing identified one known variant (c.1655G>A) and one novel deep intronic variant (c.450+38C>A) in a WMS4 patient with classic ocular and skeletal phenotypes; splicing assays confirmed the intronic variant induces abnormal pre-mRNA processing and frameshift. Conclusions: Our findings expand ADAMTS17’s mutational spectrum, underscore the value of integrating whole-genome sequencing with splicing validation, and provide critical insights for WMS4 molecular diagnosis.

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