Protein truncation test of LYST reveals heterogenous mutations in patientswith Chediak-Higashi syndrome

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder in wh ich an immune deficiency occurs in association with pigmentation abnormalit ies. Most patients who do not undergo bone marrow transplantation die of a lymphoproliferative syndrome, though some patients with CHS have a relative ly milder clinical course of the disease. The large size of the LYST gene, defective in CHS, has made it difficult to screen for mutations in a large number of patients. Only 8 mutations have been identified so far, and all l ead to a truncated LYST protein. We conducted protein truncation tests on t his gene in 8 patients with CHS. Different LYST mutations were identified i n all subjects through this approach, strengthening the observation of a hi gh frequency of truncated LYST proteins as the genetic cause of CHS. (C) 2000 by The American Society of Hematology.