Ataxia‑telangiectasia with a novel ATM gene mutation and Burkitt leukemia: A case report

Ye,Fanghua; Chai,Wenwen; Yang,Minghua; Xie,Min; Yang,Liangchun

doi:10.3892/mco.2018.1721

Ataxia‑telangiectasia with a novel ATM gene mutation and Burkitt leukemia: A case report

Authors:
- Fanghua Ye
- Wenwen Chai
- Minghua Yang
- Min Xie
- Liangchun Yang
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Affiliations: Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Nuclear Medicine, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: September 17, 2018 https://doi.org/10.3892/mco.2018.1721
Pages: 493-498

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Abstract

Ataxia‑telangiectasia (A‑T) is an infrequent autosomal recessive disorder that involves multiple systems and is characterized by progressive cerebellar ataxia, oculocutaneous telangiectasias, radiosensitivity, immune deficiency with recurrent respiratory infections, and a tendency to develop lymphoid malignancies. A‑T is caused by mutations in the ATM gene, with >1,000 mutations reported to date and gradually increasing in number. Patients with A‑T have an increased incidence of cancers. The aim of the present study was to retrospectively review the case of a patient who presented at the age of 5 years with cerebellar ataxia without telangiectasia, and was diagnosed with Burkitt leukemia by bone marrow biopsy and molecular testing at the age of 7 years at the Xiangya Hospital of Central South University (Changsha, China). The patient received chemotherapy with the pediatric CCCG‑BNHL‑2015 regimen (R4 group) and achieved a complete remission after 2 courses. However, recurrent respiratory infections and thrombosis occurred during chemotherapy. The diagnosis of A‑T was confirmed by uncovering two variants of the ATM gene, including c.742C>T (p.R248X; rs730881336) in exon 7 and c.6067‑c.6068 ins GAGGGAAGAT in exon 41 by whole‑exome sequencing. Unfortunately, the patient's parents refused follow‑up treatment and he succumbed to recurrent severe infections 4 months after the diagnosis of Burkitt leukemia. The diagnosis of A‑T may be challenging, as its phenotype can be incomplete early in the course of the disease. Detailed medical history, characteristic clinical manifestations and increasingly developed exome sequencing techniques may be helpful in diagnosing this rare disease. Management should be based on multidisciplinary guidance and other treatment options must be investigated in the future.

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1	Boder E and Sedgwick RP: Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. Pediatrics. 21:526–554. 1958.PubMed/NCBI
2	McKinnon PJ: ATM and the molecular pathogenesis of ataxia telangiectasia. Annu Rev Pathol. 7:303–321. 2012. View Article : Google Scholar : PubMed/NCBI
3	Gatti RA: Ataxia-telangiectasia. Dermatol Clin. 13:1–6. 1995. View Article : Google Scholar : PubMed/NCBI
4	Gatti RA: The inherited basis of human radiosensitivity. Acta Oncol. 40:702–711. 2001. View Article : Google Scholar : PubMed/NCBI
5	Swift M, Sholman L, Perry M and Chase C: Malignant neoplasms in the families of patients with ataxia-telangiectasia. Cancer Res. 36:209–215. 1976.PubMed/NCBI
6	Huang Y, Yang L, Wang J, Yang F, Xiao Y, Xia R, Yuan X and Yan M: Twelve novel Atm mutations identified in Chinese ataxia telangiectasia patients. Neuromolecular Med. 15:536–540. 2013. View Article : Google Scholar : PubMed/NCBI
7	Jeddane L, Ailal F, Dubois-d'Enghien C, Abidi O, Benhsaien I, Kili A, Chaouki S, Kriouile Y, El Hafidi N, Fadil H, et al: Molecular defects in Moroccan patients with ataxia-telangiectasia. Neuromolecular Med. 15:288–294. 2013. View Article : Google Scholar : PubMed/NCBI
8	Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO and Lederman HM: Ataxia telangiectasia: A review. Orphanet J Rare Dis. 11:1592016. View Article : Google Scholar : PubMed/NCBI
9	Su Y and Swift M: Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 133:770–778. 2000. View Article : Google Scholar : PubMed/NCBI
10	Teive HA, Moro A, Moscovich M, Arruda WO, Munhoz RP, Raskin S and Ashizawa T: Ataxia-telangiectasia-A historical review and a proposal for a new designation: ATM syndrome. J Neurol Sci. 355:3–6. 2015. View Article : Google Scholar : PubMed/NCBI
11	Chun HH and Gatti RA: Ataxia-telangiectasia, an evolving phenotype. DNA Repair (Amst). 3:1187–1196. 2004. View Article : Google Scholar : PubMed/NCBI
12	Gatti RA, Becker-Catania S, Chun HH, Sun X, Mitui M, Lai CH, Khanlou N, Babaei M, Cheng R, Clark C, et al: The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone. Clin Rev Allergy Immunol. 20:87–108. 2001. View Article : Google Scholar : PubMed/NCBI
13	Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA and Lederman HM: Immunodeficiency and infections in ataxia-telangiectasia. J Pediatr. 144:505–511. 2004. View Article : Google Scholar : PubMed/NCBI
14	Krauthammer A, Lahad A, Goldberg L, Sarouk I, Weiss B, Somech R, Soudack M and Pessach IM: Elevated IgM levels as a marker for a unique phenotype in patients with Ataxia telangiectasia. BMC Pediatr. 18:1852018. View Article : Google Scholar : PubMed/NCBI
15	Mitui M, Bernatowska E, Pietrucha B, Piotrowska-Jastrzebska J, Eng L, Nahas S, Teraoka S, Sholty G, Purayidom A, Concannon P and Gatti RA: ATM gene founder haplotypes and associated mutations in Polish families with ataxia-telangiectasia. Ann Hum Genet. 69:657–664. 2005. View Article : Google Scholar : PubMed/NCBI
16	Nakamura K, Du L, Tunuguntla R, Fike F, Cavalieri S, Morio T, Mizutani S, Brusco A and Gatti RA: Functional characterization and targeted correction of ATM mutations identified in Japanese patients with ataxia-telangiectasia. Hum Mutat. 33:198–208. 2012. View Article : Google Scholar : PubMed/NCBI
17	Reiman A, Srinivasan V, Barone G, Last JI, Wootton LL, Davies EG, Verhagen MM, Willemsen MA, Weemaes CM, Byrd PJ, et al: Lymphoid tumours and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumours. Br J Cancer. 105:586–591. 2011. View Article : Google Scholar : PubMed/NCBI
18	Suarez F, Mahlaoui N, Canioni D, Andriamanga C, d'Enghien Dubois C, Brousse N, Jais JP, Fischer A, Hermine O and Stoppa-Lyonnet D: Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: A report from the French national registry of primary immune deficiencies. J Clin Oncol. 33:202–208. 2015. View Article : Google Scholar : PubMed/NCBI
19	Moin M, Aghamohammadi A, Kouhi A, Tavassoli S, Rezaei N, Ghaffari SR, Gharagozlou M, Movahedi M, Purpak Z, Ghazi Mirsaeid B, et al: Ataxia-telangiectasia in Iran: Clinical and laboratory features of 104 patients. Pediatr Neurol. 37:21–28. 2007. View Article : Google Scholar : PubMed/NCBI
20	Perlman S, Becker-Catania S and Gatti RA: Ataxia-telangiectasia: Diagnosis and treatment. Semin Pediatr Neurol. 10:173–182. 2003. View Article : Google Scholar : PubMed/NCBI
21	Choi M, Kipps T and Kurzrock R: ATM mutations in cancer: Therapeutic implications. Mol Cancer Ther. 15:1781–1791. 2016. View Article : Google Scholar : PubMed/NCBI
22	Schoenaker MH, Suarez F, Szczepanski T, Mahlaoui N and Loeffen JL: Treatment of acute leukemia in children with ataxia telangiectasia (A-T). Eur J Med Genet. 59:641–646. 2016. View Article : Google Scholar : PubMed/NCBI
23	van Os NJH, Haaxma CA, van der Flier M, Merkus PJFM, van Deuren M, de Groot IJM, Loeffen J, van de Warrenburg BPC and Willemsen MAAP; A-T Study Group, : Ataxia-telangiectasia: Recommendations for multidisciplinary treatment. Dev Med Child Neurol. 59:680–689. 2017. View Article : Google Scholar : PubMed/NCBI
24	Bhatt JM, Bush A, van Gerven M, Nissenkorn A, Renke M, Yarlett L, Taylor M, Tonia T, Warris A, Zielen S, et al: ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia. Eur Respir Rev. 24:565–581. 2015. View Article : Google Scholar : PubMed/NCBI