Werner Syndrome (WRN) MCQ — NEET PG Practice Question | NEETPGAI
Werner Syndrome (WRN)
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stethoscope Medicine
A 28-year-old Indian male presents with premature graying of hair, bilateral cataracts, scleroderma-like skin changes, and recurrent ankle ulcers. He has short stature and normal pubertal development was delayed. Genetic testing reveals biallelic loss-of-function mutations in the gene located at the locus marked **B** in the diagram. Which of the following best explains the cellular basis for his accelerated-aging phenotype?
A. Impaired bloom syndrome protein function causing defective homologous recombination
B. Genomic instability and accelerated telomere attrition due to loss of DNA helicase and exonuclease activities
C. Defective lamin A/C protein synthesis leading to nuclear envelope disorganization
D. Loss of RECQL4 helicase activity resulting in replication fork stalling
Explanation
Why "Genomic instability and accelerated telomere attrition due to loss of DNA helicase and exonuclease activities" is right
The WRN gene on chromosome 8p12 encodes a unique RecQ-family helicase with dual 3'→5' DNA helicase AND 3'→5' exonuclease activities — a combination not found in other human RecQ helicases. Biallelic loss-of-function mutations in WRN cause Werner syndrome ("adult progeria"), an autosomal recessive segmental progeroid disorder. The loss of these enzymatic activities impairs DNA replication, telomere maintenance, homologous recombination, and base-excision repair, directly producing genomic instability and accelerated telomere attrition. This cellular dysfunction drives replicative senescence and the characteristic accelerated-aging phenotype—premature graying, cataracts, skin atrophy, and elevated malignancy risk—seen in this patient. (Harrison 21e Ch 470; Robbins 10e Ch 7)
Why each distractor is wrong
Defective lamin A/C protein synthesis leading to nuclear envelope disorganization: This describes Hutchinson-Gilford progeria (LMNA mutations on chromosome 1q22), which presents in early childhood with severe growth failure and death in the early teens—not the adolescent-onset, adult phenotype of Werner syndrome.
Impaired bloom syndrome protein function causing defective homologous recombination: BLM (Bloom syndrome) is encoded on chromosome 15q26 (marked C), not chromosome 8p12. Bloom syndrome presents with growth retardation, immunodeficiency, and cancer predisposition but lacks the characteristic scleroderma-like skin changes and ankle ulcers of Werner syndrome.
Loss of RECQL4 helicase activity resulting in replication fork stalling: RECQL4 is located on chromosome 8q24 (marked D) and is associated with Rothmund-Thomson syndrome, which presents with photosensitivity, poikiloderma, and juvenile cataracts—a distinct differential diagnosis from Werner syndrome.
High-YieldNEET PG
Werner syndrome = WRN (8p12) = dual helicase + exonuclease = genomic instability + telomere attrition = adult-onset progeria with scleroderma, cataracts, ulcers, and mesenchymal malignancies.
Harrison 21e Ch 470; Robbins 10e Ch 7
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