Background: Chediak-Higashi syndrome (CHS) is a rare, autosomal, recessive lysosomal disorder with hematological and immunologic abnormalities; however, stem-cell transplantation from a matched or related donor may be curative. Many mutations of the CHS1/LYST gene have been reported to date. We report a novel nonsense mutation of the CHS1/LYST gene in 3 Omani patients.
Methods and Results: Three patients from 2 different families presented with clinical and laboratory features of CHS and a history of death of a previous sibling because of a severe illness, suggestive of the accelerated phase of CHS. Giant granules were present in the myeloid cell lines. Before the stem-cell transplant, the first patient underwent gene sequencing of all exons of the lysosome trafficking regulator (CHS1/LYST) gene and revealed a nonsense mutation in exon 5 (c.925C>T, p.R309X). Subsequently, upon presentation, the second and third patients’ direct gene sequencing of exon 5 revealed the same mutation.
Conclusions: We report a nonsense mutation in exon 5 (c.925C>T, p.R309X). This supports the allelic heterogeneity of CHS and is in line with most reported mutation types that lead to a truncated protein. Identification of the mutation type will facilitate timely diagnosis, management, and family counseling for those with affected children in Oman.
Departments of *Child Health
†Hematology, Sultan Qaboos University Hospital, Muscat, Oman
The authors declare no conflict of interest.
Reprints: Salem Al-Tamemi, MD, FRCPC, Department of Child Health, Sultan Qaboos University Hospital, P.O. Box 96, PC 123 SQU, Muscat, Oman (e-mails: firstname.lastname@example.org; email@example.com).
Received March 13, 2013
Accepted August 20, 2013