A novel nucleotide substitution in the 5′ untranslated region of ANKRD26 gene is associated with inherited thrombocytopenia: a report of two new families
Inherited thrombocytopenias (IT) constitute a rare etiology of thrombocytopenia and consist of a heterogenous group of hemostatic disorders caused by molecular defects in over 30 genes . Approximately 18% of inherited thrombocytopenias are caused by monoallelic point mutations in ankyrin repeat domain 26 gene (ANKRD26), also termed thrombocytopenia-2 (THC2 OMIM 188000), with autosomal dominant transmission and increased predisposition for myeloid neoplasms . We describe two IT cases presenting during pregnancy, one of whom harbored a novel, pathogenic nucleotide substitution in ANKRD26 gene 5′ untranslated region (UTR).
A 32-year-old woman was evaluated for chronic thrombocytopenia, platelet counts ranging from 39 to 50 × 109/L, associated with easy bruising. Thrombocytopenia had been recognized early during her first pregnancy at age 23, platelet count declining to 21 × 109/L during gestation, without response to high-dose corticosteroids and IVIG for...
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Conflict of interest
The authors declare that they have no conflicts of interest.
Informed consent was obtained from all individual participants in the study.
- 1.Balduini A, Raslova H, Di Buduo CA, Donada A, Ballmaier M, Germeshausen M, Balduini CL (2018) Clinic, pathogenic mechanisms and drug testing of two inherited thrombocytopenias, ANKRD26-related thrombocytopenia and MYH9-related diseases. Eur J Med Genet 61(11):715–722. https://doi.org/10.1016/j.ejmg.2018.01.014 CrossRefGoogle Scholar
- 3.Noris P, Perrotta S, Seri M, Pecci A, Gnan C, Loffredo G, Pujol-Moix N, Zecca M, Scognamiglio F, De Rocco D, Punzo F, Melazzini F, Scianguetta S, Casale M, Marconi C, Pippucci T, Amendola G, Notarangelo LD, Klersy C, Civaschi E, Balduini CL, Savoia A (2011) Mutations in ANKRD26 are responsible for a frequent form of inherited thrombocytopenia: analysis of 78 patients from 21 families. Blood 117(24):6673–6680. https://doi.org/10.1182/blood-2011-02-336537 CrossRefGoogle Scholar
- 4.Noris P, Biino G, Pecci A, Civaschi E, Savoia A, Seri M, Melazzini F, Loffredo G, Russo G, Bozzi V, Notarangelo LD, Gresele P, Heller PG, Pujol-Moix N, Kunishima S, Cattaneo M, Bussel J, De Candia E, Cagioni C, Ramenghi U, Barozzi S, Fabris F, Balduini CL (2014) Platelet diameters in inherited thrombocytopenias: analysis of 376 patients with all known disorders. Blood 124(6):e4–e10. https://doi.org/10.1182/blood-2014-03-564328 CrossRefPubMedCentralGoogle Scholar
- 5.Pippucci T, Savoia A, Perrotta S, Pujol-Moix N, Noris P, Castegnaro G, Pecci A, Gnan C, Punzo F, Marconi C, Gherardi S, Loffredo G, De Rocco D, Scianguetta S, Barozzi S, Magini P, Bozzi V, Dezzani L, Di Stazio M, Ferraro M, Perini G, Seri M, Balduini CL (2011) Mutations in the 5' UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. Am J Hum Genet 88(1):115–120. https://doi.org/10.1016/j.ajhg.2010.12.006 CrossRefPubMedCentralGoogle Scholar
- 6.Noris P, Favier R, Alessi MC, Geddis AE, Kunishima S, Heller PG, Giordano P, Niederhoffer KY, Bussel JB, Podda GM, Vianelli N, Kersseboom R, Pecci A, Gnan C, Marconi C, Auvrignon A, Cohen W, Yu JC, Iguchi A, Miller Imahiyerobo A, Boehlen F, Ghalloussi D, De Rocco D, Magini P, Civaschi E, Biino G, Seri M, Savoia A, Balduini CL (2013) ANKRD26-related thrombocytopenia and myeloid malignancies. Blood 122(11):1987–1989. https://doi.org/10.1182/blood-2013-04-499319 CrossRefGoogle Scholar
- 7.Marquez R, Hantel A, Lorenz R, Neistadt B, Wong J, Churpek JE, Mardini NA, Shaukat I, Gurbuxani S, Miller JL, Godley LA (2014) A new family with a germline ANKRD26 mutation and predisposition to myeloid malignancies. Leuk Lymphoma 55(12):2945–2946. https://doi.org/10.3109/10428194.2014.903476 CrossRefPubMedCentralGoogle Scholar
- 9.Perez Botero J, Chen D, He R, Viswanatha DS, Majerus JA, Coon LM, Nguyen PL, Reichard KK, Oliveira JL, Tefferi A, Gangat N, Pruthi RK, Patnaik MM (2016) Clinical and laboratory characteristics in congenital ANKRD26 mutation-associated thrombocytopenia: a detailed phenotypic study of a family. Platelets 27(7):712–715. https://doi.org/10.3109/09537104.2016.1171305 CrossRefGoogle Scholar
- 10.Ferrari S, Lombardi AM, Putti MC, Bertomoro A, Cortella I, Barzon I, Girolami A, Fabris F (2017) Spectrum of 5'UTR mutations in ANKRD26 gene in patients with inherited thrombocytopenia: c.-140C>G mutation is more frequent than expected. Platelets 28(6):621–624. https://doi.org/10.1080/09537104.2016.1267337 CrossRefGoogle Scholar
- 11.Bluteau D, Balduini A, Balayn N, Currao M, Nurden P, Deswarte C, Leverger G, Noris P, Perrotta S, Solary E, Vainchenker W, Debili N, Favier R, Raslova H (2014) Thrombocytopenia-associated mutations in the ANKRD26 regulatory region induce MAPK hyperactivation. J Clin Invest 124(2):580–591. https://doi.org/10.1172/JCI71861 CrossRefPubMedCentralGoogle Scholar
- 12.Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405. https://doi.org/10.1182/blood-2016-03-643544 CrossRefGoogle Scholar
- 14.Pecci A, Gresele P, Klersy C, Savoia A, Noris P, Fierro T, Bozzi V, Mezzasoma AM, Melazzini F, Balduini CL (2010) Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. Blood 116(26):5832–5837. https://doi.org/10.1182/blood-2010-08-304725 CrossRefGoogle Scholar