title: Low incidence of ADAMTS13 missense mutation R1060W in adult Egyptian patients with thrombotic thrombocytopenic purpura.
abstract: Thrombotic thrombocytopenic purpura (TTP) is an acute life-threatening disorder, characterized by thrombocytopenia, microangiopathic hemolytic anemia, widespread microvascular thrombi and consequent clinical sequelae due to ischemic organ damage. TTP is most commonly associated with deficiency or inhibition of von Willebrand factor-cleaving protease (ADAMTS13) activity. ADAMTS13 mutations and polymorphisms have been reported in childhood congenital TTP, but their significance in adult-onset TTP is still under investigation. Two mutations stand out: the single base insertion 4143insA in exon 29 and the missense mutation R1060W in exon 24 have both been observed in several unrelated families, mainly in adult-onset TTP, and over a wide geographic area. Our objective in this study is to identify the prevalence of R1060W missense mutation in exon 24 ADAMTS13 in a sample of adult Egyptian TTP patients. Thirty-one adult-onset TTP patients were included in this study, with a male/female ratio of 1:4. Twenty-six cases (84%) presented with acute idiopathic TTP, 2 cases were drug abusers and 3 cases were pregnant. None of the study cases provided a history of suspicious TTP symptoms during childhood (2 cases gave a history of episodes of thrombocytopenia during childhood). All cases showed statistically significant decreased ADAMTS13 activity compared to normal controls (p < 0.001). The study revealed a high statistical difference regarding the ADAMTS13 inhibitor level in primary versus secondary cases (p = 0.003). None of our Egyptian cases or of the healthy normal controls are positive for exon 24 missense mutation. Larger studies and regional and national TTP registries are recommended.
authors.affiliation: Department of Clinical Pathology, University of Cairo, Cairo, Egypt.
authors.forename: Maha H
authors.initials: MH
authors.lastname: El Sissy
authors.forename: A Abd
authors.initials: AA
authors.lastname: El Hafez
authors.forename: A H
authors.initials: AH
authors.lastname: El Sissy
mesh_terms: D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics*; D000071120:ADAMTS13 Protein; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D004534:Egypt / Q000453:epidemiology; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011247:Pregnancy; D011697:Purpura, Thrombotic Thrombocytopenic / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human