Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis type 3

Journal of Medical Genetics

Volumn 48, Issue 5, 2011, Pages 343-352

  Sieni, Elena ^a   Cetica, Valentina ^a   Santoro, Alessandra ^b   Beutel, Karin ^a,c   Mastrodicasa, Elena ^d   Meeths, Marie ^e   Ciambotti, Benedetta ^a   Brugnolo, Francesca ^a   zur Stadt, Udo ^f   Pende, Daniela ^g   Moretta, Lorenzo ^h   Griffiths, Gillian M ⁱ   Henter, Jan Inge ^e   Janka, Gritta ^c   Aricó, Maurizio ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

^b AO Ospedali Riuniti Villa Sofia Cervello   (Italy)

^c UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^d Ospedale SM della Misericordia   (Italy)

^e KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^f Research Institute Children's Cancer Center   (Germany)

^g UNIVERSITY OF GENOA   (Italy)

^h G GASLINI INSTITUTE   (Italy)

ⁱ ADDENBROOKE S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MEMBRANE PROTEIN; MUNC13-4 PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CHILD; FAMILIAL DISEASE; FEMALE; FEVER; GENE DELETION; GENE INSERTION; GENE MUTATION; GENOTYPE; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; HUMAN; HYPERFERRITINEMIA; INFANT; MAJOR CLINICAL STUDY; MALE; MISSENSE MUTATION; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SPLENOMEGALY; THROMBOCYTOPENIA;

ADOLESCENT; AGE OF ONSET; CELL DEGRANULATION; CHILD; CHILD, PRESCHOOL; CYTOTOXICITY, IMMUNOLOGIC; FEMALE; GENE ORDER; GENETIC ASSOCIATION STUDIES; GENOTYPE; HUMANS; INFANT; INFANT, NEWBORN; KILLER CELLS, NATURAL; LYMPHOHISTIOCYTOSIS, HEMOPHAGOCYTIC; MALE; MEMBRANE PROTEINS; MUTATION; PHENOTYPE;

EID: 79955540994     PISSN: 00222593     EISSN: 14686244     Source Type: Journal    
DOI: 10.1136/jmg.2010.085456     Document Type: Article

References (42)

1. Aricó M, Janka G, Fischer A, Henter JI, Blanche S, Elinder G, Martinetti M, Rusca MP. Hemophagocytic lymphohistiocytosis. Report of 122 children from the International Registry. FHL Study Group of the Histiocyte Society. Leukemia 1996;10:197-203.
2. Henter JI, Samuelsson-Horne A, Aricó M, Egeler RM, Elinder G, Filipovich AH, Gadner H, Imashuku S, Komp D, Ladisch S, Webb D, Janka G; Histocyte Society. Treatment of hemophagocytic lymphohistiocytosis with HLH-94 immunochemotherapy and bone marrow transplantation. Blood 2002;100:2367-73.
3. Mahlaoui N, Ouachee-Chardin M, de Saint Basile G, Neven B, Picard C, Blanche S, Fischer A. Immunotherapy of familial hemophagocytic lymphohistiocytosis with antithymocyte globulins: a single-center retrospective report of 38 patients. Pediatrics 2007;120:e622-8.
4. Jabado N, de Graeff-Meeder ER, Cavazzana-Calvo M, Haddad E, Le Deist F, Benkerrou M, Dufourcq R, Caillat S, Blanche S, Fischer A. Treatment of familial hemophagocytic lymphohistiocytosis with bone marrow transplantation from HLA genetically nonidentical donors. Blood 1997;90:4743-8.
5. Horne A, Janka G, Egeler MR, Gadner H, Imashuku S, Ladisch S, Locatelli F, Montgomery SM, Webb D, Winiarski J, Filipovich AH, Henter JI; Histiocyte Society. Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis. Br J Haematol 2005;129:622-30.
6. Baker KS, Filipovich AH, Gross TG, Grossman WJ, Hale GA, Hayashi RJ, Kamani NR, Kurian S, Kapoor N, Ringdén O, Eapen M. Unrelated donor hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis. Bone Marrow Transplant 2008;42:175-80.
7. Cooper N, Rao K, Goulden N, Webb D, Amrolia P, Veys P. The use of reducedintensity stem cell transplantation in haemophagocytic lymphohistiocytosis and Langerhans cell histiocytosis. Bone Marrow Transplant 2008;42(Suppl 2):S47-50.
8. Cesaro S, Locatelli F, Lanino E, Porta F, Di Maio L, Messina C, Prete A, Ripaldi M, Maximova N, Giorgiani G, Rondelli R, Aricó M, Fagioli F. Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP). Haematologica 2008;93:1694-701.
9. Aricó M, Allen M, Brusa S, Clementi R, Pende D, Maccario R, Moretta L, Danesino C. Haemophagocytic lymphohistiocytosis: proposal of a diagnostic algorithm based on perforin expression. Br J Haematol 2002;119:180-8.
10. Henter JI, Elinder G, Ost A. Diagnostic guidelines for hemophagocytic lymphohistiocytosis. The FHL Study Group of the Histiocyte Society. Semin Oncol 1991;18:29-33.
11. Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, Ladisch S, McClain K, Webb D, Winiarski J, Janka G. HLH-2004: diagnostic and therapeutic guidelines for Hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31.
12. Perez N, Virelizier JL, Arenzana-Seisdedos F, Fischer A, Griscelli C. Impaired natural killer activity in lymphohistiocytosis syndrome. J Pediatr 1984;104: 569-73.
13. Aricó M, Nespoli L, Maccario R, Montagna D, Bonetti F, Caselli D, Burgio GR. Natural cytotoxicity impairment in familial haemophagocytic lymphohistiocytosis. Arch Dis Child 1988;63:292-6.
14. Schneider EM, Lorenz I, Muller-Rosenberger M, Steinbach G, Kron M, Janka-Schaub GE. Hemophagocytic lymphohistiocytosis is associated with deficiencies of cellular cytolysis but normal expression of transcripts relevant to killer-cell-induced apoptosis. Blood 2002;100:2891-8.
15. Farquhar JW, Claireaux AE. Familial haemophagocytic reticulosis. Arch Dis Child 1952;27:519-25.
16. Ohadi M, Lalloz MR, Sham P, Zhao J, Dearlove AM, Shiach C, Kinsey S, Rhodes M, Layton DM. Localization of a gene for familial hemophagocytic lymphohistiocytosis at chromosome 9q21.3-22 by homozygosity mapping. Am J Hum Genet 1999;64:165-71.
17. Dufurcq-Lagelouse R, Jabado N, Le Deist F, Stéphan JL, Souillet G, Bruin M, Vilmer E, Schneider M, Janka G, Fischer A, de Saint Basile G. Linkage of familial hemophagocytic lymphohistiocytosis to 10q21-22 and evidence for heterogeneity. Am J Hum Genet 1999;64:172-9.
18. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA, Henter JI, Bennett M, Fischer A, de Saint Basile G, Kumar V. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 1999;286:1957-9.
19. Clementi R, zur Stadt U, Savoldi G, Varotto S, Conter V, De Fusco C, Notarangelo LD, Schneider M, Klersy C, Janka G, Danesino C, Aricó M. Six novel mutations in the PRF1 gene in children with haemophagocytic lymphohistiocytosis. J Med Genet 2001;38:643-6.
20. Risma KA, Frayer RW, Filipovich AH, Sumegi J. Aberrant maturation of mutant perforin underlies the clinical diversity of hemophagocytic lymphohistiocytosis. J Clin Invest 2006;116:182-92.
21. Ueda I, Morimoto A, Inaba T, Yagi T, Hibi S, Sugimoto T, Sako M, Yanai F, Fukushima T, Nakayama M, Ishii E, Imashuku S. Characteristic perforin gene mutations of haemophagocytic lymphohistiocytosis patients in Japan. Br J Haematol 2003;121:503-10.
22. Feldmann J, Le Deist F, Ouachée-Chardin M, Certain S, Alexander S, Quartier P, Haddad E, Wulffraat N, Casanova JL, Blanche S, Fischer A, de Saint Basile G. Functional consequences of perforin gene mutations in 22 patients with familial haemophagocytic lymphohistiocytosis. Br J Haematol 2002;117:965-72.
23. Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C, Lambert N, Ouachee-Chardin M, Chedeville G, Tamary H, Minard-Colin V, Vilmer E, Blanche S, Le Deist F, Fischer A, de Saint Basile G. Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell 2003;115:461-73.
24. zur Stadt U, Schmidt S, Kasper B, Beutel K, Diler AS, Henter JI, Kabisch H, Schneppenheim R, Nürnberg P, Janka G, Hennies HC. Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 to chromosome 6q24 and identification of mutations in syntaxin 11. Hum Mol Genet 2005;14:827-34.
25. Bryceson YT, Rudd E, Zheng C, Edner J, Ma D, Wood SM, Bechensteen AG, Boelens JJ, Celkan T, Farah RA, Hultenby K, Winiarski J, Roche PA, Nordenskjöld M, Henter JI, Long EO, Ljunggren HG. Defective cytotoxic lymphocyte degranulation in syntaxin-11 deficient familial hemophagocytic lymphohistiocytosis (FHL4) patients. Blood 2007;110:1906-15.
26. zur Stadt U, Rohr J, Seifert W, Koch F, Grieve S, Pagel J, Strauss J, Kasper B, Nürnberg G, Becker C, Maul-Pavicic A, Beutel K, Janka G, Griffiths G, Ehl S, Hennies HC. Familial Hemophagocytic Lymphohistiocytosis Type 5 (FHL-5) Is Caused by Mutations in Munc18-2 and Impaired Binding to Syntaxin 11. Am J Hum Genet 2009;85:482-92.
27. Côte M, Ménager MM, Burgess A, Mahlaoui N, Picard C, Schaffner C, Al-Manjomi F, Al-Harbi M, Alangari A, Le Deist F, Gennery AR, Prince N, Cariou A, Nitschke P, Blank U, El-Ghazali G, Ménasché G, Latour S, Fischer A, de Saint Basile G. Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells. J Clin Invest 2009;119:3765-73.
28. Trizzino A, zur Stadt U, Ueda I, Risma K, Janka G, Ishii E, Beutel K, Sumegi J, Cannella S, Pende D, Mian A, Henter JI, Griffiths G, Santoro A, Filipovich A, Aricó M; Histiocyte Society HLH Study group. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. J Med Genet 2008;45:15-21.
29. Santoro A, Cannella S, Bossi G, Gallo F, Trizzino A, Pende D, Dieli F, Bruno G, Stinchcombe JC, Micalizzi C, De Fusco C, Danesino C, Moretta L, Notarangelo LD, Griffiths GM, Aricó M. Novel Munc13-4 mutations in children and young adult patients with haemophagocytic lymphohistiocytosis. J Med Genet 2006;43: 953-60.
30. Marcenaro S, Gallo F, Martini S, Santoro A, Griffiths GM, Aricó M, Moretta L, Pende D. 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.
31. Santoro A, Cannella S, Trizzino A, Bruno G, De Fusco C, Notarangelo LD, Pende D, Griffiths GM, Aricó M. Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. Haematologica 2008;93:1086-90.
32. Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G, Hennies HC. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat 2006;27:62-8.
33. Rudd E, Bryceson YT, Zheng C, Edner J, Wood SM, Ramme K, Gavhed S, Gürgey A, Hellebostad M, Bechensteen AG, Ljunggren HG, Fadeel B, Nordenskjöld M, Henter JI. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. J Med Genet 2008;45:134-41.
34. Crozat K, Hoebe K, Ugolini S, Hong NA, Janssen E, Rutschmann S, Mudd S, Sovath S, Vivier E, Beutler B. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J Exp Med 2007;204:853-63.
35. Filipovich AH. Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology Am Soc Hematol Educ Program 2009:127-31.
36. Ménasché G, Feldmann J, Fischer A, de Saint Basile G. Primary hemophagocytic syndromes point to a direct link between lymphocyte cytotoxicity and homeostasis. Immunol Rev 2005;203:165-79.
37. Horne AC, Trottestam H, Aricó M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI; Histiocyte Society. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol 2008;140:327-35.
38. Cetica V, Pende D, Griffiths GM, Aricó M. Molecular basis of familial hemophagocytic lymphohistiocytosis. Haematologica 2010;95:538-41.
39. Ueda I, Ishii E, Morimoto A, Ohga S, Sako M, Imashuku S. Correlation between phenotypic heterogeneity and gene mutational characteristics in familial hemophagocytic lymphohistiocytosis (FHL). Pediatr Blood Cancer 2006;46:482-8.
40. Yoon HS, Kim HJ, Yoo KH, Sung KW, Koo HH, Kang HJ, Shin HY, Ahn HS, Kim JY, Lim YT, Bae KW, Lee KO, Shin JS, Lee ST, Chung HS, Kim SH, Park CJ, Chi HS, Im HJ, Seo JJ. UNC13D is the predominant causative gene with recurrent splicing mutations in Korean patients with familial hemophagocytic lymphohistiocytosis. Haematologica 2010;95:622-6.
41. Wheeler RD, Cale CM, Cetica V, Aricó M, Gilmour KC. A novel assay for investigation of suspected familial haemophagocytic lymphohistiocytosis. Br J Haematol 2010;150:727-30.
42. Kogawa K, Lee SM, Villanueva J, Marmer D, Sumegi J, Filipovich AH. Perforin expression in cytotoxic lymphocytes from patients with hemophagocytic lymphohistiocytosis and their family members. Blood 2002;99:61-6.