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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5)
Blood, Volume 119, No. 25, Year 2012
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Description
Familial hemophagocytic lymphohistiocytosis (FHL) is a genetically determined hyperinflammatory syndrome caused by uncontrolled immune response mediated by T-lymphocytes, natural killer (NK) cells, and macrophages. STXBP2 mutations have recently been associated with FHL5. To better characterize the genetic and clinical spectrum of FHL5, we analyzed a cohort of 185 patients with suspected FHL for mutations in STXBP2. We detected biallelic mutations in 37 patients from 28 families of various ethnic origins. Missense mutations and mutations affecting 1 of the exon 15 splice sites were the predominant changes detectable in this cohort. Patients with exon 15 splice-site mutations (n = 13) developed clinical manifestations significantly later than patients with other mutations (median age, 4.1 year vs 2 months) and showed less severe impairment of degranulation and cytotoxic function of NK cells and CTLs. Patients with FHL5 showed several atypical features, including sensorineural hearing deficit, abnormal bleeding, and, most frequently, severe diarrhea that was only present in early-onset disease. In conclusion, we report the largest cohort of patients with FHL5 so far, describe an extended disease spectrum, and demonstrate for the first time a clear genotype-phenotype correlation. © 2012 by The American Society of Hematology.
Authors & Co-Authors
Pagel, Julia
Germany, Hamburg
Research Institute Children's Cancer Center Hamburg
Beutel, Karin
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Germany, Munster
Universitätsklinikum Münster
Lehmberg, Kai
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Koch, Florian
Germany, Hamburg
Research Institute Children's Cancer Center Hamburg
Maul-Pavicic, Andrea
Germany, Freiburg Im Breisgau
Universität Freiburg
Rohlfs, Anna Katharina
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Al-Jefri, Abdullah Hussain
Saudi Arabia, Riyadh
King Faisal Specialist Hospital and Research Centre
Beier, Rita
Germany, Hannover
Hannover Medical School
Ousager, Lilian Bomme
Denmark, Odense
Odense Universitetshospital
Ehlert, Karoline
Germany, Munster
Universitätsklinikum Münster
Gross-Wieltsch, Ute
Germany, Stuttgart
Klinikum Stuttgart Olgahospital
Jorch, Norbert
Germany, Bielefeld
Gilead Children's Hospital
Kremens, Bernhard
Germany, Duisburg
Universität Duisburg-essen
Pekrun, Arnulf
Germany, Bremen
Prof. Hess Children's Hospital
Sparber-Sauer, Monika
Germany, Ulm
Universität Ulm
Mejstrikova, Ester
Czech Republic, Prague
Charles University
Wawer, Angela
Germany, Munich
Technische Universität München
Ehl, Stephan R.
Germany, Freiburg Im Breisgau
Universität Freiburg
Zur Stadt, Udo
Germany, Hamburg
Research Institute Children's Cancer Center Hamburg
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Janka, Gritta
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Statistics
Citations: 142
Authors: 20
Affiliations: 14
Identifiers
Doi:
10.1182/blood-2011-12-398958
ISSN:
00064971
Research Areas
Genetics And Genomics
Study Design
Cohort Study