INTRODUCTION: 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.
INTRODUCTION: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.
Authors: Jan-Inge Henter; Annacarin Horne; Maurizio Aricó; R Maarten Egeler; Alexandra H Filipovich; Shinsaku Imashuku; Stephan Ladisch; Ken McClain; David Webb; Jacek Winiarski; Gritta Janka Journal: Pediatr Blood Cancer Date: 2007-02 Impact factor: 3.167
Authors: E Rudd; K Göransdotter Ericson; C Zheng; Z Uysal; A Ozkan; A Gürgey; B Fadeel; M Nordenskjöld; J-I Henter Journal: J Med Genet Date: 2006-04 Impact factor: 6.318
Authors: Yenan T Bryceson; Eva Rudd; Chengyun Zheng; Josefine Edner; Daoxin Ma; Stephanie M Wood; Anne Grete Bechensteen; Jaap J Boelens; Tiraje Celkan; Roula A Farah; Kjell Hultenby; Jacek Winiarski; Paul A Roche; Magnus Nordenskjöld; Jan-Inge Henter; Eric O Long; Hans-Gustaf Ljunggren Journal: Blood Date: 2007-05-24 Impact factor: 22.113
Authors: Isaura P Sánchez; Lucía C Leal-Esteban; Jesús A Álvarez-Álvarez; Camilo A Pérez-Romero; Julio C Orrego; Malyive L Serna; Yadira Coll; Yolanda Caicedo; Edwin Pardo-Díaz; Jacques Zimmer; Jack J Bleesing; José L Franco; Claudia M Trujillo-Vargas Journal: J Clin Immunol Date: 2012-03-22 Impact factor: 8.317