Novel Syntaxin 11 Gene (STX11) Mutation in Three Argentinean Patients with Hemophagocytic Lymphohistiocytosis
- 171 Downloads
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease with major diagnostic and therapeutic difficulties, basically comprising two different conditions: primary and secondary forms. Recent advances regarding molecular diagnosis may be useful to distinguish from one another, especially in sporadic cases starting in early infancy.
Materials and Methods
In this report, we evaluated three Argentinean patients with clinical suspicion of HLH, but without family history. We excluded mutations in the perforin gene but identified in the three patients a novel homozygous deletion (c. 581_584delTGCC; p.Leu194ProfsX2) in the gene-encoding syntaxin 11 (STX11), causing a premature termination codon.
Results and Conclusion
Each parent from the three unrelated families resulted heterozygous for this deletion confirming the diagnosis of familial hemophagocytic lymphohistiocytosis type 4. Patients shared the same single-nucleotide polymorphism profile in STX11 gene, and genotyping at ten microsatellites surrounding this gene support the presence of a single-haplotype block carrying the novel mutation.
KeywordsFamilial hemophagocytic lymphohistiocytosis primary immunodeficiency syntaxin 11 gene founder mutation
The study was supported by Agencia Nacional de Promoción Científica y Tecnológica (PICT2004 No. 21235). We wish to thank Verónica Goris for the expert handling of patient samples and Marianela Sanz for technical assistance in the detection of NK activity and CD107a.
- 14.Rudd E, Ericson KG, Zheng C, Uysal Z, Özkan A, Gürgey A, et al. Spectrum and clinical implications of syntaxin 11 gene mutations in familial haemophagocytic lymphohistiocytosis: association with disease-free remissions and haematopoietic malignancies. J Med Genet. 2006;43:e14.CrossRefPubMedGoogle Scholar
- 18.Yancoski J, Rocco C, Bernasconi A, Oleastro M, Bezrodnik L, Vrátnica C, et al. A 475 years-old founder effect involving IL12RB1: a highly prevalent mutation conferring Mendelian susceptibility to mycobacterial diseases in European descendants. Infect Genet Evol. 2009;9:574–80.CrossRefPubMedGoogle Scholar
- 23.Marcenaro S, Gallo F, Martini S, Santoro A, Griffiths GM, Aricó M, et al. Analysis of natural killer-cell function in familial hemophagocytic lymphohistiocytosis (FHL): defective CD107a surface expression heralds Munc13–4 defect and discriminates between genetic subtypes of the disease. Blood. 2006;108:2316–23.CrossRefPubMedGoogle Scholar