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.
| Original language | English |
|---|---|
| Journal | Journal of Pediatric Hematology/Oncology |
| Volume | 36 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 |
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Keywords
- albinism
- Chediak-Higashi syndrome
- CHS1/LYST gene
- immunodeficiency
- Oman
ASJC Scopus subject areas
- Hematology
- Oncology
- Pediatrics, Perinatology, and Child Health
Cite this
Chediak-Higashi syndrome : Novel mutation of the CHS1/LYST gene in 3 Omani patients. / Al-Tamemi, Salem; Al-Zadjali, Shoaib; Al-Ghafri, Fahad; Dennison, David.
In: Journal of Pediatric Hematology/Oncology, Vol. 36, No. 4, 2014.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Chediak-Higashi syndrome
T2 - Novel mutation of the CHS1/LYST gene in 3 Omani patients
AU - Al-Tamemi, Salem
AU - Al-Zadjali, Shoaib
AU - Al-Ghafri, Fahad
AU - Dennison, David
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - albinism
KW - Chediak-Higashi syndrome
KW - CHS1/LYST gene
KW - immunodeficiency
KW - Oman
UR - http://www.scopus.com/inward/record.url?scp=84899923542&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899923542&partnerID=8YFLogxK
U2 - 10.1097/MPH.0000000000000025
DO - 10.1097/MPH.0000000000000025
M3 - Article
C2 - 24072239
AN - SCOPUS:84899923542
VL - 36
JO - Journal of Pediatric Hematology/Oncology
JF - Journal of Pediatric Hematology/Oncology
SN - 1077-4114
IS - 4
ER -