A 28-year-old woman presents with recurrent joint dislocations, skin hyperextensibility, and easy bruising. Genetic testing reveals a mutation in COL3A1 (type III collagen). All of the following are true regarding type III collagen EXCEPT:

Explanation

## Type III Collagen: Structure and Clinical Significance ### Overview of Collagen Types **High-Yield:** There are at least 28 collagen types, but the most clinically relevant are: | Collagen Type | Composition | Major Tissues | Clinical Disorders | |---|---|---|---| | **Type I** | [α1(I)]₂α2(I) | Bone, tendon, skin, ligaments, scar tissue | Osteogenesis imperfecta | | **Type II** | [α1(II)]₃ | Cartilage, vitreous humor, intervertebral disc | Achondrogenesis, chondrodysplasias | | **Type III** | [α1(III)]₃ | Blood vessels, hollow organs, skin dermis, fetal skin | vEDS (vascular Ehlers–Danlos) | | **Type IV** | [α1(IV)]₂α2(IV) | Basement membranes | Alport syndrome | ### Correct Statements (Options 0, 1, 2) **Key Point:** Type III collagen is a **homotrimer** composed of three identical α1(III) chains forming a [α1(III)]₃ triple helix. It is the predominant collagen in: - Blood vessel walls (especially large arteries) - Hollow organs (GI tract, bladder, uterus) - Skin dermis (especially in fetal and young skin) - Lung parenchyma **Clinical Pearl:** Mutations in **COL3A1** cause **vascular Ehlers–Danlos syndrome (vEDS)**, characterized by: - Thin, translucent skin with visible veins - Recurrent joint dislocations and hyperextensibility - **Spontaneous arterial rupture** (most life-threatening feature) - Bowel perforation - Uterine rupture during pregnancy The defective type III collagen in blood vessel walls leads to structural weakness and catastrophic vascular events. ### The Incorrect Statement (Option 3) **Warning:** Type **I** collagen is synthesized in **much larger quantities** than type III collagen in most tissues. Type I comprises ~80–90% of total body collagen by mass, while type III comprises only ~5–10%. - **Type I dominates:** bone, tendon, skin (dermis and epidermis), ligaments, scar tissue - **Type III is significant but secondary:** blood vessels, hollow organs, fetal skin The relative abundance is tissue-dependent, but globally, type I >> type III. ### Pathophysiology of vEDS ```mermaid flowchart TD A[COL3A1 mutation]:::urgent --> B[Defective α1 III chains] B --> C[Abnormal type III collagen triple helix] C --> D[Weakened blood vessel walls] D --> E[Loss of structural integrity] E --> F[Spontaneous arterial rupture]:::urgent E --> G[Bowel perforation]:::urgent E --> H[Uterine rupture in pregnancy]:::urgent C --> I[Skin hyperextensibility] C --> J[Joint hypermobility] ``` ### Differential: vEDS vs. Classical EDS | Feature | vEDS (COL3A1) | Classical EDS (COL5A1/COL5A2) | |---|---|---| | **Skin appearance** | Thin, translucent, fragile | Velvety, hyperextensible | | **Scarring** | Atrophic, poor healing | Abnormal (cigarette-paper scars) | | **Joint hypermobility** | Mild to moderate | Severe | | **Vascular risk** | **HIGH** (arterial rupture) | Low | | **Life expectancy** | Reduced (median ~50 years) | Near-normal | | **Pregnancy risk** | **Uterine rupture** | Moderate | **Mnemonic for vEDS complications: BRAVE** - **B**owel perforation - **R**upture (arterial) - **A**rterial dissection - **V**ascular events - **E**very pregnancy is high-risk