2. Academic Validation
  3. Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia

Novel G6B gene variant causes familial autosomal recessive thrombocytopenia and anemia

  • Eur J Haematol. 2017 Mar;98(3):218-227. doi: 10.1111/ejh.12819.
Motasem Melhem 1,  Mohamed Abu-Farha 2,  Dinu Antony 1,  Ashraf Al Madhoun 1,  Chiara Bacchelli 3,  Fadi Alkayal 4,  Irina AlKhairi 2,  Sumi John 5,  Mohamad Alomari 6,  Phillip L Beales 3,  Osama Alsmadi 1
Affiliations

Affiliations

  • 1 Genetics and Genomics Department, Dasman Diabetes Institute, Dasman, Kuwait.
  • 2 Biochemistry and Molecular Biology Department, Dasman Diabetes Institute, Dasman, Kuwait.
  • 3 Genetics and Genomic Medicine, UCL Institute of Child Health, London, UK.
  • 4 Pancreatic Islet Biology & Transplantation Unit, Dasman Diabetes Institute, Dasman, Kuwait.
  • 5 Integrative Informatics, Dasman Diabetes Institute, Dasman, Kuwait.
  • 6 Department of Pathology, Windsor Regional Hospital, Windsor, ON, Canada.
PMID: 27743390 DOI: 10.1111/ejh.12819
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.

Keywords

C6orf25; G6b; anemia; platelets; thrombocytopenia.

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