In human connective tissue disorders, defects in which structural protein are primarily responsible for the clinical features of Ehlers–Danlos syndrome (EDS)?

Introduction / Context:
Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility, and tissue fragility. The question tests understanding of which macromolecular component underpins these clinical manifestations.

Given Data / Assumptions:

• EDS involves weakness of connective tissues such as skin, ligaments, blood vessels, and hollow organs.
• Different EDS subtypes map to mutations in genes encoding structural proteins or modifying enzymes.
• We focus on the core structural protein affected most commonly.

Concept / Approach:
Connective tissue tensile strength depends largely on collagen fibrils. Many EDS types are caused by mutations in collagen genes (e.g., COL5A1/COL5A2 for classical EDS, COL3A1 for vascular EDS) or enzymes involved in collagen processing (e.g., lysyl hydroxylase). Therefore, defects in collagen biosynthesis, structure, or cross-linking explain the phenotype.

Step-by-Step Solution:

Verification / Alternative check:
Clinical genetics consistently associates EDS with collagen-related gene defects and abnormal collagen fibrillogenesis seen on ultrastructural studies, validating collagen as the key protein involved.

Why Other Options Are Wrong:

• Elastin: important for elasticity (e.g., in Marfan-related pathways), but not the typical cause of EDS.
• Fibrin: involved in coagulation, not connective tissue tensile strength.
• Immunoglobulins (globulins): immune proteins, unrelated to EDS structural defects.
• Keratin: structural protein of epithelia, hair, nails; keratinopathies present differently.

Common Pitfalls:
Confusing EDS with Marfan syndrome (fibrillin-1 defects) or elastinopathies; assuming “any structural protein” could explain EDS when collagen defects are central.

Final Answer:
Collagen protein