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Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia

Melhem, M; Abu-Farha, M; Antony, D; Al Madhoun, A; Bacchelli, C; Alkayal, F; AlKhairi, I; ... Alsmadi, O; + view all (2017) Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia. European Journal of Haematology , 98 (3) pp. 218-227. 10.1111/ejh.12819. Green open access

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Abstract

Objective To characterize the underlying genetic and molecular defects in a consanguineous family with lifelong blood disorder manifested with thrombocytopenia (low platelets count) and anemia. Methods Genetic linkage analysis, exome sequencing, and functional genomics were carried out to identify and characterize the defective gene. Results We identified a novel truncation mutation (p.C108*) in chromosome 6 open reading frame 25 (C6orf25) gene in this family. We also showed the p.C108* mutation was responsible for destabilizing the encoded truncated G6B protein. Unlike the truncated form, wild‐type G6B expression resulted in enhanced K562 differentiation into megakaryocytes and erythrocytes. C6orf25, also known as G6B, is an effector protein for the key hematopoiesis regulators, Src homology region 2 domain‐containing phosphatases SHP‐1 and SHP‐2. Conclusion G6B seems to act through an autosomal recessive mode of disease transmission in this family and regarded as the gene responsible for the observed hematological disorder. This inference is well supported further by in vivo evidence where similar outcomes were reported from G6b−/− and SHP1/2 DKO mouse models.

Type: Article
Title: Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ejh.12819
Publisher version: https://doi.org/10.1111/ejh.12819
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Anemia, platelets, thrombocytopenia, G6b, C6orf25
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10070859
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