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Vol. 42. Issue S1.
Pages 68-69 (October 2020)
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Vol. 42. Issue S1.
Pages 68-69 (October 2020)
PP 59
Open Access
A rare variant of dyskeratosis congenita: RTEL1 defect
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C. Coskun1,*, S. Unal2, N. Akarsu2
1 Hacettepe University, Department of Pediatric Hematology, Ankara, Turkey
2 Hacettepe University, Research Center for Fanconi Anemia and Other Inherited Bone Marrow Failure Syndromes, Ankara, Turkey
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Objective: Dyskeratosis congenita (DC) is a rare hereditary disorder characterized by bone marrow failure, malignancy predisposition and skin findings. As the disease progresses, patients may develop pulmonary fibrosis, esophageal stenosis, urethral stenosis and liver cirrhosis. Herein, we present a patient who was referred with a diagnosis Diamond Blackfan anemia and was diagnosed to have dyskeratosis congenita on whole exome sequencing (WES).

Case report: A 18 month-old girl who was initially transfused at the age of three-months old and was on mothly transfusion programme, was referred to our center for molecular work-up with a diagnosis of DBA. There was second degree consanguinity between parents. On physical examination, body weight: 8.7kg (5th percentile) height: 44cm (<3rd percentile) was measured. Cubitus valgus was seen with camptodactyly. Liver and spleen were not palpable. Complete blood count showed hemoglobin (Hb) 7.9g/dL, mean corpuscular volume (MCV) 104.1fl, white blood count 6.9×109/L, absolute neutrophil count 1.3×109/L, platelet count 682×109/L, reticulocytes 2% and peripheral smear showed hypochromia and macrocytosis in erythrocytes. Biochemical parameters, globin electrophoresis, vitamin B12 and folic acid levels were normal. Parvovirus B19 was negative. ADA2 enzyme level was determined as 24 U/L (5–20U/L). Steroid was started at the age of 18 month-old with a clinical suspicion of DBA. She became transfusion independent after steroid initiation. WES analysis for DBA from the patient revealed RTEL1 gene mutation (c.1368G> T p.1trp456Cys). This mutation was found compatible with DC and no other mutations in DBA related genes were detected, including CNV analyses for large deletions. Steroid was ceased gradually and she did not require further transfusions after complete cessation.

Results: In dyskeratosis congenita cases where the disease does not follow classical presentation, the use of genetic testing confirms the diagnosis at an early stage and reduces morbidity and mortality due to the disease. WES is helpful to detect such cases.

Conclusion: Various genes such as DKC1, CTC1, RTEL1, TERF1, TINF2, TERC have been found to be responsible for DKC. RTEL1 is a DNA helicase necessary for telomere replication and stability. With the understanding of the molecular basis of the disease, patients with hematological findings at the time of diagnosis and those without skin findings were also identified. In our case, signs of bone marrow failure were observed primarily and no changes in nail dystrophy, leukoplakia and skin pigmentation and neurological findings were detected. In cases where the disease does not follow classical presentation, the use of genetic testing confirms the diagnosis at an early stage and reduces morbidity and mortality due to the disease. WES is helpful to detect such cases.

Idiomas
Hematology, Transfusion and Cell Therapy
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