Mutations in the Chediak-Higashi syndrome gene (CHS1) indicate requirement for the complete 3801 amino acid CHS protein

Chediak-Higashi syndrome (CHS) is a rare, usually fatal, autosomalrecessive disorder characterized by severe immunologic defects, reducedpigmentation, progressive neurologic dysfunction and a bleeding diathesis.The hallmark of CHS is giant organelles and giant granules in manydifferent cell types, most likely the result of defective trafficking ofspecific organellar and granular proteins necessary for the normal genesis,structure or function of these cytoplasmic components. The CHS1 gene hasrecently been identified and shown to be homologous to the beige locus ofthe mouse; however, there has been disagreement as to the length of thefunctional CHS1 mRNA and protein. Here we report homozygous CHS1 genemutations in two of the original probands we used to map the gene to1q42-q44. One of these, a frameshift at codon 3197, supports our assertionthat the functional CHS protein is a predicted 3801 amino acid polypeptideencoded by a 13.5 kb mRNA.