E207K mutation of low-density lipoprotein receptor in familial hypercholesterolemia

Area of Science:

• Genetics
• Cardiology
• Biochemistry

Background:

• Familial hypercholesterolemia (HeFH) is an inherited disorder characterized by high LDL cholesterol levels.
• Premature coronary artery disease (CAD) is a significant complication of untreated HeFH.
• Genetic mutations in the low-density lipoprotein receptor (LDLR) gene are a common cause of HeFH.

Observation:

• A 36-year-old man presented with premature CAD and heterozygous familial hypercholesterolemia (HeFH).
• Hypercholesterolemia was prevalent in his mother, wife, and three children.
• Genetic analysis identified a specific G to A substitution (c.682G>A) in the LDLR gene.

Findings:

• The identified mutation, Glu(207) to Lys (E207K), was located in the ligand-binding domain of the LDLR.
• This E207K mutation was present in the affected family members, inherited from the mother and passed to the children.
• The proband's wife did not carry this specific LDLR mutation, despite having hypercholesterolemia.

Implications:

• The genetic identification of the E207K LDLR mutation confirms the cause of HeFH in this family.
• Early diagnosis through genetic testing allows for targeted interventions.
• Prompt treatment can mitigate the risk of premature cardiovascular events like CAD.