A Novel Syntaxin 11 Gene (STX11) Mutation c.650T>C, p.Leu217Pro, in a Korean Child With Familial Hemophagocytic Lymphohistiocytosis
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We report the first Far Eastern case of a Korean child with familial hemophagocytic lymphohistiocytosis (HLH) caused by a novel syntaxin 11 (STX11) mutation. A 33-month-old boy born to non-consanguineous Korean parents was admitted for intermittent fever lasting one week, pancytopenia, hepatosplenomegaly, and HLH in the bone marrow. Under the impression of HLH, genetic study revealed a novel homozygous missense mutation of STX11: c.650T>C, p.Leu217Pro. Although no large deletion or allele drop was identified, genotype analysis demonstrated that the homozygous c.650T>C may have resulted from the duplication of a maternal (unimaternal) chromosomal region and concurrent loss of the other paternal allele, likely caused by meiotic errors such as two crossover events. A cumulative study of such novel mutations and their effects on specific protein interactions may deepen the understanding of how abnormal STX1 expression results in deficient cytotoxic function.
Abstract
We report the first Far Eastern case of a Korean child with familial hemophagocytic lymphohistiocytosis (HLH) caused by a novel syntaxin 11 (STX11) mutation. A 33-month-old boy born to non-consanguineous Korean parents was admitted for intermittent fever lasting one week, pancytopenia, hepatosplenomegaly, and HLH in the bone marrow. Under the impression of HLH, genetic study revealed a novel homozygous missense mutation of STX11: c.650T>C, p.Leu217Pro. Although no large deletion or allele drop was identified, genotype analysis demonstrated that the homozygous c.650T>C may have resulted from the duplication of a maternal (unimaternal) chromosomal region and concurrent loss of the other paternal allele, likely caused by meiotic errors such as two crossover events. A cumulative study of such novel mutations and their effects on specific protein interactions may deepen the understanding of how abnormal STX1 expression results in deficient cytotoxic function.
참고문헌 (11)
- zur Stadt U, "Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11", Hum Mol Genet, 14, pp.827~834 (2005)
- zur Stadt U, "Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A", Hum Mutat, 27, pp.62~68 (2006)
- Henter JI, "HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis", Pediatr Blood Cancer, 48, pp.124~131 (2007)
- Horne A, "Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis", Br J Haematol, 143, pp.75~83 (2008)
- Sepulveda FE, "Distinct severity of HLH in both human and murine mutants with complete loss of cytotoxic effector PRF1, RAB27A, and STX11", Blood, 121, pp.595~603 (2013)
- Yoon HS, "UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis", Haematologica, 95, pp.2010~2095 (2010)
- Yamamoto K, "Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people", J Hum Genet, 50, pp.600~603 (2005)
- Zhizhuo H, "Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis", Pediatr Blood Cancer, 58, pp.410~414 (2012)
- Marsh RA, "STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America", Pediatr Blood Cancer, 55, pp.134~140 (2010)
- Danielian S, "Novel syntaxin 11 gene (STX11) mutation in three Argentinean patients with hemophagocytic lymphohistiocytosis", J Clin Immunol, 30, pp.330~337 (2010)
- Engel E, "A new genetic concept: uniparental disomy and its potential effect, isodisomy", Am J Med Genet, 6, pp.137~143 (1980)