title: Bleeding disorders in Lowe syndrome patients: evidence for a link between OCRL mutations and primary haemostasis disorders.
abstract: Lowe syndrome (LS) is a rare X-linked disorder caused by mutations in the oculocerebrorenal gene (OCRL), encoding OCRL, a phosphatidylinositol 5-phosphatase with a RhoGAP domain. An abnormal rate of haemorrhagic events was found in a retrospective clinical survey. Herein, we report the results of exploration of haemostasis in six LS patients. All patients had normal coagulation tests but prolonged closure times (CTs) in the PFA-100 system. Healthy donors' blood samples incubated with a RhoA kinase inhibitor had prolonged CTs. This suggests that an aberrant RhoA pathway in platelets contributes to CT prolongation and primary haemostasis disorders in LS.
authors.affiliation: AP-HP Hôpital Necker, Laboratoire d'Hématologie, Paris, France. dom.lasne@nck.aphp.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Lasne
authors.forename: Geneviève
authors.initials: G
authors.lastname: Baujat
authors.forename: Tristan
authors.initials: T
authors.lastname: Mirault
authors.forename: Joël
authors.initials: J
authors.lastname: Lunardi
authors.forename: Françoise
authors.initials: F
authors.lastname: Grelac
authors.forename: Marion
authors.initials: M
authors.lastname: Egot
authors.forename: Rémi
authors.initials: R
authors.lastname: Salomon
authors.forename: Christilla
authors.initials: C
authors.lastname: Bachelot-Loza
mesh_terms: D000293:Adolescent; D001780:Blood Coagulation Tests; D002648:Child; D002675:Child, Preschool; D020690:GTPase-Activating Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D020141:Hemostatic Disorders / Q000209:etiology* / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009800:Oculocerebrorenal Syndrome / Q000150:complications* / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D010744:Phosphoric Monoester Hydrolases; C075695:OCRL protein, human