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Investigating the Genetic Etiology of Disease in a Patient with Aplastic Anemia

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IRC-SET 2021

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Abstract

This study investigates the molecular basis of a male patient presenting with aplastic anemia (AA) and related symptoms of macrocytosis and mild thrombocytopenia. In addition, this patient also presents symptoms not usually found in AA patients, such as fatty liver, liver cirrhosis with portal hypertension, diffuse cerebral and cerebellar atrophy, and congenital left sensorineural hearing loss. As such, it is hypothesized that the patient has AA that is secondary to inherited bone marrow failure syndromes related to telomere biology disorders. Thus, to identify the underlying genetic cause of the disease, relative telomere length (RTL) of proband and family members was determined by qPCR, followed by identification of disease-causing variants through next-generation sequencing of the proband. The proband has a RTL of 0.11 (− 5.96 SD) which is shorter than the 1st percentile (− 2.33 SD). As RTL analysis indicates significant telomere shortening in the patient, it is likely that the patient has a telomere biology disorder. 8 variants in genes (DKC1, ATXN3, PTPRQ, ABCB4, DIAPH3, TBP, PARP1) associated with our patient’s phenotype, 2 of which were previously reported and were also shortlisted as potential candidates. However, upon curation, these variants were found to be of uncertain significance, and the genetic cause of our patient’s condition remains elusive. Nonetheless, we were able to confirm that the patient had significant shortening of telomeres.

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Author information

Authors and Affiliations

  1. Raffles Institution, Bishan, Singapore

    Beverly Low Ying Tong, Lee Shi Mei Charmaine & Tay Jia Ying

  2. Department of Paediatrics, National University of Singapore, Singapore, Singapore

    Grace Tan Li Xuan, Liu Chun Ping & Lai Poh San

  3. Department of Lab Medicine, National University Hospital, Singapore, Singapore

    Eng Soo Yap

  4. Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore

    Tung Moon Ley

Authors
  1. Beverly Low Ying Tong
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  2. Lee Shi Mei Charmaine
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  4. Grace Tan Li Xuan
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Correspondence to Beverly Low Ying Tong .

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Editors and Affiliations

  1. International Researchers Club, Singapore, Singapore

    Huaqun Guo

  2. Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore

    Hongliang Ren

  3. Singapore Institute of Technology, Singapore, Singapore

    Victor Wang

  4. Department of Information Systems Technology and Design, Singapore University of Technology and Design, Singapore, Singapore

    Eyasu Getahun Chekole

  5. Agency for Science Technology and Research, Experimental Drug Development Centre, Singapore, Singapore

    Umayal Lakshmanan

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Tong, B.L.Y. et al. (2022). Investigating the Genetic Etiology of Disease in a Patient with Aplastic Anemia. In: Guo, H., Ren, H., Wang, V., Chekole, E.G., Lakshmanan, U. (eds) IRC-SET 2021. Springer, Singapore. https://doi.org/10.1007/978-981-16-9869-9_4

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