Comprehensive genetic screening for vascular Ehlers-Danlos syndrome through an amplification-based next-generation...

Area of Science:

• Genetics
• Vascular Biology
• Connective Tissue Disorders

Background:

• Vascular Ehlers-Danlos syndrome (vEDS) is a life-threatening hereditary connective tissue disorder.
• Diagnosis relies on identifying heterozygous variants in the COL3A1 gene.
• Limited data exists on vEDS in Asian populations.

Purpose of the Study:

• To investigate the genetic basis of vEDS in an Asian cohort.
• To evaluate the efficacy of amplification-based next-generation sequencing for detecting COL3A1 variants and copy number variations.

Main Methods:

• Analysis of 429 patients with suspected hereditary connective tissue disorders (HCTDs) using custom gene panels.
• Next-generation sequencing (NGS) with amplification-based methods.
• Specific evaluation of copy number variations (CNVs).

Main Results:

• 101 patients were suspected of vEDS; 33 (32.4%) had confirmed COL3A1 variants.
• COL3A1 variants were also found in two patients with Loeys-Dietz syndrome/familial thoracic aortic aneurysm and dissection.
• The majority of variants were missense substitutions (Glycine or non-Glycine), splice site alterations, nonsense variants, or deletions.

Conclusions:

• NGS with custom panels is effective for diagnosing vEDS and detecting diverse COL3A1 variants, including CNVs, in various sample types.
• This study represents the largest Asian case series for vEDS and provides valuable genetic insights into the condition within this population.