Abstract
Ataxia-telangiectasia (AT) is a rare neurodegenerative disease characterized by an early onset ataxia, oculocutaneous telangiectasia, immunodeficiency, recurrent infections, radio-sensitivity, and a predisposition to malignancy. We present the case of a child with coexistent AT and trisomy X (47,XXX). We used fluorescent in situ hybridization (FISH) to confirm that this person had 47,XXX karyotype in blood cells, bone marrow, fibroblasts, and buccal smear. Standard cytogenetic studies (not banded) were conducted on blood cells. G-banding analysis was performed on bone marrow cells at the time of the leukemia diagnosis. Flow cytometric investigation of lymphocytes and Sanger sequencing of the ATM gene were used for diagnosis confirmation and description. We report the case of an 11-year-old girl at remission after having T cell acute leukemia for 7 years with progressive signs of ataxia-telangiectasia and with additional X chromosome since birth. At the age of 2 years and 7 months, she was diagnosed with pre-T acute leukemia. From the age of four, she had gait abnormalities. AT was established at the age of seven based on clinical signs and laboratory findings (increased alpha fetoprotein—AFP [227]) and confirmed by detecting compound heterozygous truncating mutations in the ATM gene (p.Y705X and p.L2312I). These genetic findings have not been previously reported in AT and our “double hit” case demonstrates the value of careful clinical evaluation of children with an established genetic diagnosis. Measurement of AFP levels should be considered in patients with neurologic abnormalities after leukemia treatment.
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Acknowledgements
The authors are most grateful to the patient and their family members for their co-operation during this study, and for the generous donation of samples and the photo of the proband. The authors are sincerely grateful to Dr. Olga Zobikova for the comments.
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This work was funded by grants from the Belarusian Ministry of Health.
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The study was approved by the Ethical Committee of the Belarusian Research Centre for Pediatric Oncology, Hematology and Immunology. Written informed consent for sampling and processing and for the use of the photo was obtained from the patient’s parents.
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The authors declare that they have no conflicts of interest.
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Sharapova, S.O., Valochnik, A.V., Guryanova, I.E. et al. Novel biallelic ATM mutations coexist with a mosaic form of triple X syndrome in an 11-year-old girl at remission after T cell acute leukemia. Immunogenetics 70, 613–617 (2018). https://doi.org/10.1007/s00251-018-1056-4
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DOI: https://doi.org/10.1007/s00251-018-1056-4