Molecular Genetics — MCQs

Question 1: An adult tall male presents with a long arm span, pectus excavatum, and cardiac abnormalities. What is the most likely defective protein?

• A. Fibrillin (Correct Answer)
• B. Elastin
• C. Collagen
• D. Myosin
• E. Laminin

Explanation: ***Fibrillin*** - The constellation of **tall stature**, **long arm span**, **pectus excavatum**, and **cardiac abnormalities** (e.g., aortic dissection or mitral valve prolapse) is classic for **Marfan syndrome**. - Marfan syndrome is caused by a defect in the *FBN1* gene, which codes for **fibrillin-1**, a glycoprotein essential for the formation of elastic fibers in connective tissue. *Elastin* - Defects in **elastin** are associated with conditions like **supravalvular aortic stenosis** (due to **Williams syndrome**) or cutis laxa, which have different phenotypic presentations. - While both elastin and fibrillin are components of elastic fibers, the specific features of Marfan syndrome point to fibrillin as the primary defect. *Collagen* - Defects in **collagen** (especially type I, III, or V) are associated with conditions such as **osteogenesis imperfecta** (brittle bones) or **Ehlers-Danlos syndrome** (hypermobility, skin hyperextensibility). - These conditions typically present with different clinical manifestations, lacking the specific combination of features seen in this patient. *Myosin* - **Myosin** is a fibrous protein primarily involved in **muscle contraction** and is not directly implicated in widespread connective tissue disorders affecting skeletal and cardiovascular systems in this manner. - Defects in myosin are more commonly associated with various forms of **cardiomyopathy** or skeletal muscle myopathies, not Marfan-like features. *Laminin* - **Laminin** is a major component of the **basement membrane** and plays a role in cell adhesion, migration, and tissue architecture. - Laminin defects are associated with certain forms of **muscular dystrophy** (e.g., congenital muscular dystrophy) and **epidermolysis bullosa**, not the specific skeletal and cardiovascular features of Marfan syndrome.