title: [The significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis].
abstract: OBJECTIVE
  To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH).
  
  
  METHODS
  Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations.
  
  
  RESULTS
  The DNA mutations of the four families included missense mutation c.T172C (p.S58P) and non- frameshift deletions c.1083_1094del (p.361_365del), missense mutation c.C1349T (p.T450M) and frameshift mutation c.1090_1091delCT (p.T364fsX93) in PRF1 gene, missense mutation c.G2588A (p.G863D) in UNC13D gene and hemizygous mutation c.32T>G (p.I11S) in SH2D1A gene. The patients and their family members presented decreased NK cell activities. Individuals who carried mutations of PRF1 gene and SH2D1A gene showed low expression of perforin (PRF1) and signaling lymphocytic activation molecule associated protein (SAP). And the patient with UNC13D gene mutation and his family member with identical mutation showed significant reducing cytotoxic degranulation function (expression of CD107a).
  
  
  CONCLUSIONS
  Pedigree genetic screening and rapid detection of immunological parameters might play an important role in the diagnosis of primary HLH, and both of them had good consistency. As an efficient detection means, the rapid immunological detection indicators would provide reliable basis for the early diagnosis of the primary HLH.
authors.affiliation: Department of Hematology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y N
authors.initials: YN
authors.lastname: Wang
authors.forename: J S
authors.initials: JS
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: N
authors.initials: N
authors.lastname: Wei
authors.forename: L
authors.initials: L
authors.lastname: Fu
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.forename: J H
authors.initials: JH
authors.lastname: Chen
authors.forename: R J
authors.initials: RJ
authors.lastname: Pei
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D005820:Genetic Testing; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D054353:Perforin / Q000235:genetics; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C510468:PRF1 protein, human; C114953:SH2D1A protein, human; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; C507969:UNC13D protein, human; D054353:Perforin