A Rare Big Chinese Family With Thrombocytopenia 2: A Case Report and Literature Review

Abstract

Thrombocytopenia 2 (THC2) is one of the most prevalent forms of inherited thrombocytopenia. It is caused by a heterogeneous group of ANKRD26 gene mutation and shows a heterogeneous clinical and laboratory characteristics. We present a big Chinese family with 10 THC2 patients carrying c.-128G > T heterozygous substitution in the 5-untranslated region of the ANKRD26 gene. Although the platelets are fewer than 50 × 10 9 /L in 8 THC2 family members, only the proband and her son show a higher WHO bleeding score. The proband and her son are also beta-thalassemia carriers with heterozygous c.52A > T mutation of HBB, which might not be associated with the increased bleeding tendency since 3 other family members with low bleeding tendency also carried both ANKRD26 c.-128G > T and HBB c.52A > T mutations. However, the proband and her son also show hypofibrinogenaemia, which is likely the cause of their more severe clinical manifestation. HID1 c.442G > T mutation was detected not only in these two hypofibrinogenaemia family members but also in the other 8 family members with normal blood fibrinogen levels. Our study suggests that the co-occurrence of other inherited genetic conditions associated with blood coagulation might contribute to the heterogeneity of clinical and laboratory characteristics in THC2 patients. Considering the hematologic and myeloid malignancy predisposition of THC2 patients and a large population of immune thrombocytopenia in China, we urge more attention to be paid to the diagnosis of THC2 patients to avoid misdiagnosis and mistreatment.

Inherited Thrombocytopenia Caused by Germline ANKRD26 Mutation Should Be Considered in Young Patients With Suspected Myelodysplastic Syndrome

“…Multiple families with hereditary thrombocytopenia have been identified to have mutations within this same region of the 5′UTR. 7 - 18 Also, DNA sequence analysis of the APC gene demonstrated a variant of undetermined significance, which was a heterozygous sequence change located in the exon 16, c.4918 C>T.…”

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

“…The most common disease related to ANKRD26 is thrombocytopenia 2 (THC2), which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[ 7 - 9 ]. Caused by the variants in the 5’-untranslated region (UTR) of ANKRD26 , THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[ 8 , 10 ]. Due to the point mutations that occur in the 5’-UTR of ANKRD26 , its negative transcription factors (TFs), Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1), lose their repression effect[ 11 ].…”

Familial thrombocytopenia due to a complex structural variant resulting in a WAC-ANKRD26 fusion transcript

“…We study a multigenerational family impacted by congenital thrombocytopenia, resembling inherited thrombocytopenia 2 (THC2; Online Mendelian Inheritance in Man accession no. 188000; Noris et al, 2011;Pippucci et al, 2011;Tan et al, 2020;Turro et al, 2020), which is typically caused by single nucleotide variants (SNVs) that de-repress ANKRD26 expression during megakaryocytic differentiation (Bluteau et al, 2014;Marconi et al, 2017). THC2 is generally characterized by thrombocytopenia accompanied by altered hematopoiesis and predisposition to myeloid malignancies.…”