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Zorluk: OrtaGenetic and Molecular Mechanisms

A medical geneticist is reviewing the molecular pathophysiology of various inherited disorders to guide genetic counseling and targeted therapies. Understanding the exact nature of the genetic alteration is essential for predicting disease severity and managing systemic complications. Match the following clinical genetic disorders with their primary underlying molecular mechanism.

  • Cystic fibrosis (most common allele)Abnormal protein folding and premature intracellular degradation
  • AchondroplasiaConstitutive activation of a transmembrane tyrosine kinase receptor
  • Duchenne muscular dystrophyFrameshift mutation leading to a truncated, nonfunctional protein
  • Sickle cell anemiaMissense mutation promoting abnormal protein polymerization

Cevap

Cystic fibrosis matches with abnormal protein folding and intracellular degradation. Achondroplasia matches with constitutive activation of a transmembrane tyrosine kinase receptor. Duchenne muscular dystrophy matches with a frameshift mutation leading to a truncated protein. Sickle cell anemia matches with a missense mutation promoting abnormal protein polymerization.
Matching the correct molecular mechanisms relies on understanding the specific genetic pathogenesis of these classic disorders. Cystic fibrosis (delta F508) represents a defect in post-translational processing and intracellular trafficking. Achondroplasia represents a classic gain-of-function mutation altering receptor signaling dynamics. Duchenne muscular dystrophy is the quintessential example of an out-of-frame (frameshift) mutation leading to total loss of protein function. Sickle cell anemia is driven by a precise missense mutation that alters the physical properties of hemoglobin under hypoxic stress.

Adım Adım Çözüm

1
Analyze the molecular defect in Cystic fibrosis.
Identified as a CFTR folding defect.
The delta F508 mutation deletes a single phenylalanine residue, which impairs post-translational folding, resulting in targeted proteasomal degradation.
2
Analyze the molecular defect in Achondroplasia.
Identified as FGFR3 overactivation.
A specific point mutation in the FGFR3 gene causes the receptor to be continuously active without binding to fibroblast growth factor, prematurely limiting bone growth.
3
Analyze the molecular defect in Duchenne muscular dystrophy.
Identified as an out-of-frame mutation.
Unlike the milder Becker variant (in-frame), Duchenne is caused by frameshift mutations that create premature stop codons, obliterating dystrophin function.
4
Analyze the molecular defect in Sickle cell anemia.
Identified as beta-globin chain polymerization.
The substitution of a polar amino acid for a nonpolar one (valine) creates a hydrophobic pocket that drives aggregation of deoxygenated HbS molecules.

Anahtar Kavram

Molecular pathogenesis of monogenic disorders
Tahmini Süre:1m 0s
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Konular

Genetic and Molecular Mechanisms

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