The role of gene encoding collagen secretion protein (SERPINH1) in the pathogenesis of a hypermobile type of Ehlers-Danlos syndrome

Introduction: Hypermobile (hEDS) Ehlers-Danlos syndrome (EDS) is a non-inflammatory, autosomal dominant connective tissue disorder. hEDS, unlike other types of EDS, has no known genetic aetiology, so diagnosis is conducted based on a person's medical history, a physical examination, and exclusion of other types of EDS after genetic tests.

Aim: The present study was a sequencing analysis of the SERPINH1 gene and the evaluation of the potential impact of variants of this gene on their role in the aetiology of the hypermobile type of EDS.

Material and methods: The study group included 100 hEDS patients of Polish origin. The SERPINH1 gene analysis was performed on genomic DNA (gDNA). In all patients, other types of EDS or other connective tissue disorders were excluded by testing them with NGS technology.

Results: Among 100 tested patients, 4 different types of missense variants (heterozygote) were detected. All SERPINH1 alterations were classified as benign according to ACMG guidelines.

Conclusions: Mutations in the SERPINH1 gene have been described in a rare type of OI but have never been analysed in hypermobile Ehlers-Danlos syndrome. In our investigation among 100 hEDS patients, we did not identify pathogenic or likely pathogenic variants. Though only benign variants were detected, which play no role in the pathogenesis of hEDS, we should take into account mechanisms other than gene structure alterations, which may have an impact on collagen and other ECM protein transport.