Abstract Number: PB1235
Meeting: ISTH 2022 Congress
Background: Inherited thrombocytopenia (IT) related to cytoskeletal protein defects (CPD) caused by variants in genes encoding for components of the acto-myosin cytoskeleton (MYH9-RD, TUBB1-RT, ACTN1-RT, or DIAPH1-RD, among others) are increasingly recognized, and altogether, are the most frequent in our cohort of patients.
Aims: To characterize the platelet phenotype and genetic defects in 26 unrelated families with CPD-related IT, from a Portuguese unique centre.
Methods: Sixty-two patients from 26 families from the north of Portugal (9 with TUBB1-RT, 9 with ACTN1-RT, 7 with MYH9-RD and 1 with DIAPH1-RD) were included. Platelet counts and indexes [mean platelet volume (MPV) and immature platelet fraction (IPF)] were evaluated. Patients DNA were analyzed by high-throughput sequencing (HTS) using a 91-gene panel related to Hemostasis, or by Sanger sequencing. Variants classification was performed according to ACMG recommendations.
Results: Globally patients had irrelevant bleedings. Twenty-five patients from 9 families with identified variants in TUBB1, had median platelet counts 120×109/L, MPV 13.5 fL and IPF 15.2%; the variants were classified as likely-pathogenic/pathogenic in five, variants of uncertain significance (VUS) in two, and likely-benign/benign in other two families. Twenty-two patients from 9 families with identified variants in ACTN1, had median platelet counts 101×109/L, MPV 14.6 fL and IPF 26.4%; the variants were classified as likely-pathogenic/pathogenic in six families, VUS in other two families and one benign. Regarding MYH9, 14 patients from 7 families, had median platelet counts 25×109/L, MPV 23 fL and IPF 62.1%; the identified variants were classified as likely-pathogenic/pathogenic in five families, VUS in another and one likely-benign. The patient with DIAPH-RD had a causal variant already known. In total, five variants were identified for the first time.
Conclusion(s): In the presence of macrothrombocytopenia without bleeding symptoms and platelet dysfunction, CPD-related IT should be suspected. Although some platelet indexes may suggest different disorders, only genetic tests confirm the diagnosis.
To cite this abstract in AMA style:Morais S, Monteiro C, Pereira M, Gonçalves A, Gonçalves M, Lau C, Santos R, Cruz E. Clinical and mutational spectrum of inherited thrombocytopenia related to cytoskeleton protein defects. [abstract]. https://abstracts.isth.org/abstract/clinical-and-mutational-spectrum-of-inherited-thrombocytopenia-related-to-cytoskeleton-protein-defects/. Accessed September 27, 2023.
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