A Family with Meester–Loeys Syndrome Caused by a Novel Missense Variant in the BGN Gene

Résumé fourni par la source

Meester–Loeys syndrome (MLS) is an X-linked connective tissue disorder caused by pathogenic BGN variants. We describe a family carrying a novel missense variant. The index male, initially diagnosed with Ehlers–Danlos syndrome, had joint hypermobility, multiple visceral artery aneurysms, and recurrent musculoskeletal problems. A brother of the proband had an aortic root aneurysm. Female carriers had no or only minor manifestations. Studies of the aortic wall were consistent with a dysregulation of the TGF-β/SMAD pathway and assays with reporter vectors revealed reduced canonical Wnt and TGF-β activity in cell lines expressing mutant biglycan. However, patients’ dermal fibroblasts did not show consistent differences in the nuclear abundance of β-catenin or p-SMAD2/3 compared to cells from controls. This 3-generation family expands the genetic and phenotypic spectrum of MLS and underscores the importance of considering BGN testing in hypermobility syndromes to enable early surveillance and targeted management.

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