TY - JOUR T1 - ACTN1-related thrombocytopenia: identification of novel families for phenotypic characterization. JF - Blood Y1 - 2015 A1 - Bottega, Roberta A1 - Marconi, Caterina A1 - Faleschini, Michela A1 - Baj, Gabriele A1 - Cagioni, Claudia A1 - Pecci, Alessandro A1 - Pippucci, Tommaso A1 - Ramenghi, Ugo A1 - Pardini, Simonetta A1 - Ngu, Loretta A1 - Baronci, Carlo A1 - Kunishima, Shinji A1 - Balduini, Carlo L A1 - Seri, Marco A1 - Savoia, Anna A1 - Noris, Patrizia KW - Actinin KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Blood Platelets KW - Case-Control Studies KW - Child KW - Child, Preschool KW - Female KW - Gene Expression KW - Genotype KW - Heterozygote KW - Humans KW - Male KW - Middle Aged KW - Mutation, Missense KW - Pedigree KW - Phenotype KW - Platelet Count KW - Severity of Illness Index KW - Thrombocytopenia KW - Thrombopoiesis KW - Thrombopoietin AB -
Inherited thrombocytopenias (ITs) are a heterogeneous group of syndromic and nonsyndromic diseases caused by mutations affecting different genes. Alterations of ACTN1, the gene encoding for α-actinin 1, have recently been identified in a few families as being responsible for a mild form of IT (ACTN1-related thrombocytopenia; ACTN1-RT). To better characterize this disease, we screened ACTN1 in 128 probands and found 10 (8 novel) missense heterozygous variants in 11 families. Combining bioinformatics, segregation, and functional studies, we demonstrated that all but 1 amino acid substitution had deleterious effects. The clinical and laboratory findings of 31 affected individuals confirmed that ACTN1-RT is a mild macrothrombocytopenia with low risk for bleeding. Low reticulated platelet counts and only slightly increased serum thrombopoietin levels indicated that the latest phases of megakaryopoiesis were affected. Given its relatively high frequency in our cohort (4.2%), ACTN1-RT has to be taken into consideration in the differential diagnosis of ITs.
VL - 125 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25361813?dopt=Abstract ER -