ATP6V1B2 – Zimmermann-Laband syndrome 2

The ATP6V1B2 gene encodes the B2 subunit of the vacuolar H+-ATPase and is implicated in autosomal dominant multisystemic syndromes. Heterozygous de novo missense variants, notably c.1454G>C (p.Arg485Pro), were identified in 2 unrelated probands with classic features of gingival hyperplasia, nail hypoplasia and intellectual disability in Zimmermann-Laband syndrome 2 (2 probands) ([PMID:25915598]). No additional familial segregation has been reported, limiting the genetic case series for ZLS2.

Structural analysis predicts that p.Arg485Pro disrupts V-ATPase complex assembly, supporting a dominant-negative mechanism ([PMID:25915598]). While truncating alleles such as p.Arg506Ter and other variants expand phenotypic overlap with DDOD and DOORS syndromes, evidence specific to ZLS2 remains confined to isolated de novo missense events. ATP6V1B2 genetic testing is recommended in individuals with ZLS2-like features, though further segregation and functional studies are needed to confirm pathogenicity and clarify mechanism.

References

• Nature Genetics • 2015 • Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome PMID:25915598

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