title: The genetics of the alternative pathway of complement in the pathogenesis of HELLP syndrome.
abstract: OBJECTIVE
  Recent preliminary evidence suggests that gene mutations in the alternative pathway of complement may play a crucial role in the pathogenesis of HELLP syndrome. To verify this hypothesis, a consecutive series of women who developed the syndrome was screened for variants in alternative pathway genes.
  
  
  METHODS
  The coding sequences and intron-exon boundaries of the complement factor H (CFH), complement factor I (CFI), Membrane Cofactor Protein (MCP), complement factor B (CFB) and C3 were sequenced in 33 women with a diagnosis of HELLP syndrome.
  
  
  RESULTS
  Three patients carried heterozygotic variants - two in CFI and one in MCP. One of the two CFI mutations, was previously described as an unremarkable polymorphism. Conversely, computational analyses for the remaining two cases suggest that they may have a functional impact.
  
  
  CONCLUSIONS
  The present study confirms that the alternative pathway of complement may play a role in the pathogenesis of HELLP syndrome. However, its overall contribution to the determinism of the syndrome is less relevant than initially reported.
authors.affiliation: Department Obstet-Gynecol, Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Crovetto
authors.forename: Nicolò
authors.initials: N
authors.lastname: Borsa
authors.forename: Barbara
authors.initials: B
authors.lastname: Acaia
authors.forename: Carla
authors.initials: C
authors.lastname: Nishimura
authors.forename: Kathy
authors.initials: K
authors.lastname: Frees
authors.forename: Richard J H
authors.initials: RJ
authors.lastname: Smith
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.forename: Roberta
authors.initials: R
authors.lastname: Palla
authors.forename: Massimo
authors.initials: M
authors.lastname: Cugno
authors.forename: Silvana
authors.initials: S
authors.lastname: Tedeschi
authors.forename: Pierangela
authors.initials: P
authors.lastname: Castorina
authors.forename: Edgardo
authors.initials: E
authors.lastname: Somigliana
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ardissino
authors.forename: Luigi
authors.initials: L
authors.lastname: Fedele
mesh_terms: D000328:Adult; D017668:Age of Onset; D017244:Complement Factor I / Q000235:genetics; D003170:Complement Pathway, Alternative / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005865:Gestational Age; D017359:HELLP Syndrome / Q000453:epidemiology / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D051916:Membrane Cofactor Protein / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011262:Pregnancy Trimester, Second / Q000276:immunology; D011263:Pregnancy Trimester, Third / Q000276:immunology; D012189:Retrospective Studies
chemical_list: D051916:Membrane Cofactor Protein; D017244:Complement Factor I