Elsevier

Gene

Volume 715, 5 October 2019, 143957
Gene

Short communication
Case report of a novel MPIG6B gene mutation in a Chinese boy with pancytopenia and splenomegaly

https://doi.org/10.1016/j.gene.2019.143957Get rights and content

Highlights

  • A Chinese boy presenting with splenomegaly and hemocytopenia was identified a homozygous frameshift mutation in MPIG6B gene.

  • It’s a new form of MPIG6B variation that has never been reported in public database before.

  • Due to a germline mutation, stem cell transplantation was recommended first.

Abstract

MPIG6B has orthologous physiological effects in human and mice, which regulates platelet production and function. For this reason, germline loss-of-function mutations in this gene cause congenital thrombocytopenia that is associated with bone marrow fibrosis, organomegaly and subsequent anemia. This was described in a consanguineous Arabian family with a novel truncation mutation (p.C108*) in chromosome 6, open reading frame 25 gene, also known as MPIG6B. In our case, we identified a homozygous frameshift variation (c.392delC,p.P134Lfs*10) in a ten-month-old boy presenting with signs of pallor, splenomegaly and resistant hemocytopenia. Interestingly, this is a new form of a MPIG6B variation, which could disrupt the effector protein for the key hematopoiesis regulators. This report adds to the growing number of mutations causing complex clinical manifestations associated with pancytopenia and splenomegaly in children.

Introduction

Pancytopenia is a relatively common phenomenon in the hematology department (Abel et al., 2012), defined as a decrease in all three blood cell lineages. It is commonly caused in the patients suffering from thrombocytopenia, anemia and infection. Thrombocytopenia is characterized by low platelets counts that are below normal levels, meanwhile anemia is caused by a reduction in hemoglobin contents and/or low red blood cell (RBC) counts compared to healthy individuals (Morris et al., 2010; Weinzierl and Arber, 2013). These can result from many reasons, especially developmental molecular impairments, like DNA damage in the bone marrow progenitor cells, which leads to abnormal cellular division and/or differentiation.

The megakaryocyte-specific immunoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptor, G6b-B, sometimes called C6orf25 or MPIG6B, is located in the class III region of the human MHC complex, a region known to contain many genes associated with the immune system (Geer et al., 2018; de Vet et al., 2001). It acts as a critical regulator of megakaryocytic function and platelet production. Mice lacking G6b-B showed severe macrothrombocytopenia and bleeding diathesis due to abnormal platelet function. In addition, megakaryocytes in G6b-B-deficient mice dysfunction in proplatelet formation (Mazharian et al., 2012).

Siblings from a consanguineous Arab family were reported to suffer from significant lifelong reduced platelet counts in association with an anemic phenotype due to germline loss-of-function mutations in G6b-B (Melhem et al., 2016). In our case, we first described a Chinese boy with a deletion mutation (c.392delC) located at exon 2 of the MPIG6B gene, resulting in a frameshift of amino acid (p.P134Lfs*10).

Section snippets

Case presentation

Upon admission the patient was a 10-month-old boy who suffered from pallor, splenomegaly and hemocytopenia lasting more than 7 months. On physical examination, he exhibited pin-point bleeding on his skin; moreover, his spleen was palpable 3 cm below the left iliac fossa. Other system examination findings were unremarkable. Laboratory tests suggested anemia with lower hemoglobin levels ranging from 70 to 90 g/L. In addition, variable thrombocytopenia was also observed in this affected patient

Discussion

In the present case report, we described the phenotype of a 10-month-old boy who presented with splenomegaly and recurrent hemocytopenia. Microscopic findings suggested severe thrombocytopenia with increased numbers of giant platelets and anemia with deformed and broken RBCs in the peripheral smear. Bone marrow biopsy suggested a hypocellular marrow associated with focal bone marrow fibrosis. Notably, we identified a germline frameshift variation (c.392delC,p.P134Lfs*10) in MPIG6B.

Conclusion

In conclusion, we present the first Chinese case with a homozygous frameshift variation (c.392delC) in MPIG6B. It shows that this mutation may lead to abnormal hematopoiesis, especially in megakaryocyte lineage. We believe that our case will contribute to an increasing number of mutation variants and complex clinical findings that are associated with pancytopenia splenomegaly in children.

Declaration of Competing Interest

We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company.

Acknowledgement

This work was supported by grants from National Science and Technology Key Projects (No. 2017ZX09304029004) as well as the Beijing Municipal Administration of Hospitals Clinical medicine Development of Special funding Support (No. ZY201404).

References (12)

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