title: Clinical and laboratory characteristics in congenital ANKRD26 mutation-associated thrombocytopenia: A detailed phenotypic study of a family.
abstract: The clinical and laboratory characteristics of patients with non-syndromic, autosomal dominant thrombocytopenia secondary to germ line ANKRD26 mutations appear to be heterogeneous. Except for a targeted molecular genotyping approach, there is no distinct clinical or laboratory phenotype that has been specifically associated with this particular gene mutation. Such heterogeneity could be due to variations in mutation and genetic background in different families. To understand the phenotypic heterogeneity, we thoroughly studied one affected family using the International Society for Thrombosis and Haemostasis bleeding assessment tool and both clinically validated standard and esoteric platelet testing (electron microscopy (EM) and flow cytometry). We found that decreased platelet aggregation with arachidonic acid and epinephrine agonists was common in affected family members. EM studies demonstrated persistent borderline low mean dense granules per platelet, decreased alpha granules and an increased canalicular network pattern in all affected members. Since these characteristics are subtle or non-pathognomonic, molecular testing for ANKRD26 mutation remains the most reliable test to render a diagnosis and should be considered when evaluating a patient or family with congenital thrombocytopenia, particularly if there is a history of myeloid neoplasms.
authors.affiliation: a Division of Hematology , Department of Medicine , Mayo Clinic, Rochester , MN , USA.
authors.forename: Juliana
authors.initials: J
authors.lastname: Perez Botero
authors.affiliation: b Special Coagulation Laboratory , Mayo Clinic, Rochester , MN , USA.|c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Chen
authors.affiliation: b Special Coagulation Laboratory , Mayo Clinic, Rochester , MN , USA.|c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.affiliation: c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Viswanatha
authors.affiliation: b Special Coagulation Laboratory , Mayo Clinic, Rochester , MN , USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Majerus
authors.affiliation: b Special Coagulation Laboratory , Mayo Clinic, Rochester , MN , USA.|c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Lea M
authors.initials: LM
authors.lastname: Coon
authors.affiliation: c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Phuong L
authors.initials: PL
authors.lastname: Nguyen
authors.affiliation: c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Reichard
authors.affiliation: c Division of Hematopathology , Department of Laboratory Medicine and Pathology , Mayo Clinic, Rochester , MN , USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Oliveira
authors.affiliation: a Division of Hematology , Department of Medicine , Mayo Clinic, Rochester , MN , USA.
authors.forename: Ayalew
authors.initials: A
authors.lastname: Tefferi
authors.affiliation: a Division of Hematology , Department of Medicine , Mayo Clinic, Rochester , MN , USA.
authors.forename: Naseema
authors.initials: N
authors.lastname: Gangat
authors.affiliation: a Division of Hematology , Department of Medicine , Mayo Clinic, Rochester , MN , USA.|b Special Coagulation Laboratory , Mayo Clinic, Rochester , MN , USA.
authors.forename: Rajiv K
authors.initials: RK
authors.lastname: Pruthi
authors.affiliation: a Division of Hematology , Department of Medicine , Mayo Clinic, Rochester , MN , USA.
authors.forename: Mrinal M
authors.initials: MM
authors.lastname: Patnaik
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010974:Platelet Aggregation; D010976:Platelet Count; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000235:genetics*; D055815:Young Adult
chemical_list: C583630:ANKRD26 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins
keywords: ANKRD26 protein; blood platelet disorders; electron microscopy; flow cytometry; platelet aggregation; thrombocytopenia