2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Discrepant Germline Genetic Testing for Inherited Bone Marrow Failure Syndrome in a Patient with Myelodysplastic Syndrome

Pdf Summary

In this case study, a 48-year-old male with myelodysplastic syndrome (MDS) and chronic thrombocytopenia was evaluated for a possible underlying inherited bone marrow failure syndrome (IBMFS). The patient had a history of thrombocytopenia since age 25 and had been previously diagnosed with immune thrombocytopenia purpura (ITP). A bone marrow examination at age 46 showed hypocellular bone marrow, leading to a diagnosis of MDS. Chromosomal abnormalities were also detected.<br /><br />Further genetic testing was performed, including germline genetic testing using peripheral blood and cultured skin fibroblast samples. There were discrepant results between the two samples, with the cultured skin fibroblast sample revealing a heterozygous, pathogenic 86.36kb deletion on chromosome 3q26.2. This deletion encompassed the whole TERC gene and exon 1 of transcript 4 of the MECOM gene, providing a diagnosis of a telomere biology disorder (TBD).<br /><br />De novo microdeletions within the MECOM locus have been associated with congenital thrombocytopenia, and heterozygous pathogenic variants in the MECOM gene can result in radioulnar synostosis with amegakaryotic thrombocytopenia. However, this case is unique as it describes a patient presenting with MDS attributed to a deletion affecting exon 1 of the MECOM gene and the entire TERC gene.<br /><br />The authors highlight the importance of selecting the appropriate sample source for germline genetic testing in patients with MDS. They advocate for the use of cultured skin fibroblasts for accurate confirmation of germline genetic variants in these patients. Additional functional studies are needed to understand the physiological impact of the identified deletion on hematopoiesis in early embryogenesis.<br /><br />Overall, this case adds to the understanding of the genetic basis of IBMFS and emphasizes the need for thorough genetic evaluation in patients with MDS to guide appropriate management and treatment decisions.

Asset Subtitle

Presenting Author - Moon Ley Tung, MBBS, MRCP (UK), FRCPath (Hematology)(UK); Co-Author - Jennifer L. Stinson, MS, LGC; Co-Author - Athena Puski, MS, LGC; Co-Author - Kyle Dillahunt, MS; Co-Author - Alpa Sidhu, MBBS, PhD;

Meta Tag

Cancer Cytogenetics

Cancer Syndromes

Genetic Testing

Genotype-Phenotype Correlations

NextGen Sequencing

Co-Author Jennifer L. Stinson, MS, LGC

Co-Author Athena Puski, MS, LGC

Co-Author Kyle Dillahunt, MS

Co-Author Alpa Sidhu, MBBS, PhD

Presenting Author Moon Ley Tung, MBBS, MRCP (UK), FRCPath (Hematology)(UK)

Keywords

case study

myelodysplastic syndrome

chronic thrombocytopenia

inherited bone marrow failure syndrome

immune thrombocytopenia purpura

bone marrow examination

chromosomal abnormalities

germline genetic testing

telomere biology disorder

MECOM gene