A 35 year old tall male from New Jersy has Marfan syndrome, an autosomal dominant disorder with features of subluxated lens of the eye, mitral valve prolapsed. The defect lies in:
**Question:** A 35 year old tall male from New Jersy has Marfan syndrome, an autosomal dominant disorder with features of subluxated lens of the eye, mitral valve prolapsed. The defect lies in:
A. Fibulin-5
B. Transforming Growth Factor-β (TGF-β)
C. connective tissue proteins
D. GLA gene
**Correct Answer:** D. GLA gene
**Core Concept:**
Marfan syndrome is a systemic connective tissue disorder with a combination of symptoms affecting various parts of the body, including the cardiovascular, ophthalmological, and skeletal systems. It is classified as an autosomal dominant disorder, meaning that a person with one mutated copy of the gene is at risk for developing the disease and can pass the mutation on to their offspring.
**Why the Correct Answer is Right:**
The correct answer lies in the **GLA gene**, which is responsible for encoding for the enzyme alpha-galactosidase A (α-Gal A). This enzyme plays a crucial role in the lysosomal breakdown of glycosaminoglycans, specifically in the degradation of heparan sulfate and dermatan sulfate. Mutations in the GLA gene lead to a deficiency in the α-Gal A enzyme, causing a buildup of glycosaminoglycans in connective tissues, leading to the characteristic features of Marfan syndrome.
**Why Each Wrong Option is Incorrect:**
A. Fibulin-5: Fibulin-5 is a protein involved in the regulation of extracellular matrix assembly and does not directly relate to the pathophysiology of Marfan syndrome.
B. Transforming Growth Factor-β (TGF-β): TGF-β is a protein that plays a role in cell signaling and tissue repair, but its direct relation to Marfan syndrome is not clear.
C. Connective tissue proteins: While connective tissue proteins are essential for proper tissue function and structure, this option is too broad, and the specific GLA gene mutation is responsible for Marfan syndrome.
**Clinical Pearl:**
Marfan syndrome can be diagnosed by various criteria, including the revised Ghent criteria. Identifying mutations in the GLA gene can help confirm the diagnosis and guide genetic counseling for the patient and their family members. Inheritance of the mutated gene increases the risk of developing Marfan syndrome, allowing healthcare professionals to anticipate the onset and severity of symptoms in affected individuals.