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


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.
Salem
S
Al-Tamemi
Shoaib
S
Al-Zadjali
Fahad
F
Al-Ghafri
David
D
Dennison
D064591:Allografts; D002609:Chediak-Higashi Syndrome / Q000235:genetics* / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D009850:Oman; D033581:Stem Cell Transplantation; D033921:Vesicular Transport Proteins / Q000235:genetics*
D018389:Codon, Nonsense; C102161:LYST protein, human; D033921:Vesicular Transport Proteins