Ann Lab Med.  2016 Mar;36(2):170-173. 10.3343/alm.2016.36.2.170.

A Novel Syntaxin 11 Gene (STX11) Mutation c.650T>C, p.Leu217Pro, in a Korean Child With Familial Hemophagocytic Lymphohistiocytosis

• Sultanova
• Kim SK
• Lee JW
• Jang PS
• Chung NG
• Cho B
• Park J
• Kim Y
• Kim M

• KMID: 2373518
• DOI: http://doi.org/10.3343/alm.2016.36.2.170

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.

Keyword

Syntaxin 11; Mutation; Hemophagocytic lymphohistiocytosis; Korean

MeSH Terms

Alleles
Amino Acid Sequence
Asian Continental Ancestry Group/*genetics
Base Sequence
Bone Marrow/metabolism
Child, Preschool
Comparative Genomic Hybridization
DNA Mutational Analysis
Genotype
Haplotypes
Homozygote
Humans
Lymphohistiocytosis, Hemophagocytic/*genetics/pathology
Male
Molecular Sequence Data
Mutation, Missense
Pedigree
Qa-SNARE Proteins/*genetics
Republic of Korea
Sequence Alignment
Qa-SNARE Proteins

Figure

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  Fig. 1 Direct sequencing analysis of syntaxin 11 gene (STX11). The proband was homozygous for a missense mutation, c.650T>C, p.Leu217Pro, his mother was heterozygous for the same mutation, and his father and sister had no mutation in the STX11. A base substitution mutation in the second codon position is indicated by the red dots.

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  Fig. 2 Pedigree and haplotype analysis with the closest markers linked to the mutation. The arrow indicates the proband. The patient's haplotype included paternal (orange) and maternal (black) types in one allele (left). The gray bar indicates an equivocal region in which the maternal and paternal genotypes were identical.

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  Fig. 3 (A) Domains of the STX11 protein with previously reported STX11 mutations (black) and the patient's novel mutation, c.650T>C (red). (B) Comparative genomic analysis. The Leu217 residue of STX11 is highly conserved across all 12 vertebrate species according to Evola (http://www.h-invitational.jp/evola/).

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