A child presents with generalized ichthyosis, recurrent skin infections, photophobia, and oculocutaneous albinism. Peripheral blood smear shows giant granules in neutrophils. What is the gene mutated in this disorder?

• A ABCA12 gene
• B WASp gene
• C RAG1/RAG2 gene
• D LYST (lysosomal trafficking regulator) gene ✓

Explanation

This is Chediak-Higashi syndrome, an autosomal recessive disorder caused by mutation of the LYST gene (chromosome 1q42), encoding a lysosomal trafficking regulator. The hallmark is giant azurophilic granules in leukocytes (fused lysosomes), leading to defective neutrophil chemotaxis and killing, recurrent pyogenic infections, partial oculocutaneous albinism, and progressive neuropathy. The accelerated phase (hemophagocytic lymphohistiocytosis) can be fatal. ABCA12 mutations cause harlequin ichthyosis.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.