ATP6V0D2 – Ehlers-Danlos syndrome

In a cohort of 69 individuals with suspected hereditary connective tissue disorders, two unrelated families exhibited an autosomal recessive syndrome characterized by cutis laxa and distinctive facial features, and ATP6V0D2 was nominated as a compelling candidate gene based on whole-exome and whole-genome sequencing (PMID:27023906). The phenotype included skin laxity with reduced recoil and dysmorphic facial gestalt overlapping classical EDS features, although hallmark joint hypermobility and vascular fragility were not fully documented. No specific pathogenic variant in ATP6V0D2 has been detailed in the publication, and segregation analysis was limited to the two probands without extended pedigree confirmation. Functional studies directly linking V-ATPase D2 dysfunction to extracellular matrix integrity or connective tissue homeostasis are currently absent. Additional replication in independent families, biochemical validation of variant effects on lysosomal acidification, and in vivo modeling are needed to establish causality. Key Take-home: ATP6V0D2 is a novel candidate for a recessive EDS-like connective tissue disorder but requires further genetic and functional validation for clinical application.

References

• Human Genetics • 2016 • Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue. PMID:27023906

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