Chediak-Higashi syndrome: novel mutation of the CHS1/LYST gene in 3 Omani patients.

Abstract

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.

• Authors: Salem Al-Tamemi, Shoaib Al-Zadjali, Fahad Al-Ghafri, David Dennison
• Journal: Journal of pediatric hematology/oncology (J Pediatr Hematol Oncol) Vol. 36 Issue 4 Pg. e248-50 (May 2014) ISSN: 1536-3678 [Electronic] United States
• PMID: 24072239 (Publication Type: Case Reports, Journal Article)

Chemical References

• Codon, Nonsense
• LYST protein, human
• Vesicular Transport Proteins

Topics

• Allografts
• Chediak-Higashi Syndrome (genetics, therapy)
• Child
• Child, Preschool
• Codon, Nonsense
• DNA Mutational Analysis
• Exons
• Female
• Humans
• Male
• Oman
• Stem Cell Transplantation
• Vesicular Transport Proteins (genetics)