Whole-exome sequencing confirmation of a novel heterozygous mutation in RUNX1 in a pregnant woman with platelet disorder

Abstract

We describe a successful pregnancy and delivery in a patient with platelet disorder. Prophylactic platelet transfusions ensured that there were no bleeding complications during and after cesarean section. Following delivery, we performed whole exome sequencing, using next generation sequencing, to analyze the DNA samples of the patient and her family, and to identify the disease-causing mutation or variant. To identify de-novo mutations systematically, we also analyzed DNA isolated from the parents of the patient and the neonate. We successfully identified a causative novel mutation c.419 G > A (p.S140N) in RUNX1 in the patient and the neonate. Mutations of RUNX1 have been reported to be associated with familial platelet disorder and with a predisposition for myelodysplasia and/or acute myeloid leukemia. The patient and the neonate require careful long-term hematological follow-up. Identification of mutations by a through whole-exome analysis using next-generation sequencing may be useful in the determination of a long-term follow-up schedule for the patient.

• Platelet disorder
• pregnancy
• FPD/AML
• RUNX1

Acknowledgements

We are grateful to Dr. Tetsuo Mitsui for helpful discussions. We appreciate the participation of the patient and her family.

Declaration of interest

This study was supported by the post-quake reconstruction support project of RIKEN Omics Science Center with RIKEN Genome Analysis Service (GeNAS), Illumina Co, and CLCBio Co. This work was supported in part by Grants-in-Aid for Scientific Research No. 22390308 and No. 21659379 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. This work was supported in part by Grants-in-Aid for the Global Center of Excellence (COE) Program from the Japan Society for the Promotion of Science. The authors declare no competing financial interests. M. O., S. T., and H. K. conceived and designed the study; M. O., S. T., K. T., W. N., and T. Y. provided study materials or patients; M. O. and S. T. collected and assembled data; M. O., S. T., S. M. and G. T. analyzed and interpreted data; and all authors wrote the manuscript.