Four people with ADAMTS6 variants point to a new connective tissue disorder
Exome and genome sequencing of a French cohort with syndromic or isolated thoracic aortic disease turned up rare damaging ADAMTS6 variants in four unrelated people. The variants impaired ADAMTS6 secretion and catalytic activity, which disrupted processing of fibrillin-1 and fibrillin-2 and left microfibrils disorganized. Patient-derived fibroblasts and Adamts6-deficient mice showed parallel defects. Presentations ranged from early-onset multisystem disease, with cardiovascular, skeletal, craniofacial and neurodevelopmental abnormalities, to isolated adult-onset aortic aneurysm, the 2026 study reported.
A substantial share of heritable thoracic aortic aneurysm and dissection cases still has no genetic explanation. ADAMTS6 is now a candidate gene, though the evidence rests on four patients, cultured cells and mice.
Written by the Genomes desk from the primary source cited and linked above and checked against it. Research use only; not medical advice. Corrections: [email protected].