A boy has reticulated skin pigmentation, nail dystrophy, oral leukoplakia and develops aplastic anaemia at age 12. Genetic testing identifies a mutation in DKC1. The encoded protein, dyskerin, is an essential component of which enzymatic complex?

• A The spliceosome removing introns from pre-mRNA
• B Telomerase, the reverse transcriptase that maintains chromosome ends ✓
• C DNA polymerase alpha involved in lagging strand synthesis
• D Ribonucleotide reductase generating deoxyribonucleotides

Explanation

Dyskeratosis congenita is caused by DKC1 mutations affecting dyskerin, a core component of the telomerase ribonucleoprotein complex alongside TERT and the TERC RNA template. Defective telomere maintenance causes premature exhaustion of stem cell compartments, producing mucocutaneous triad plus bone marrow failure and cancer predisposition. Spliceosome and polymerase defects present as other syndromes, and ribonucleotide reductase inhibition causes replication stress rather than progressive marrow failure over years.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.