title: New diagnosis of atypical ataxia-telangiectasia in a 17-year-old boy with T-cell acute lymphoblastic leukemia and a novel ATM mutation.
abstract: Ataxia-telangiectasia (A-T) is an autosomal recessive chromosome breakage disorder caused by mutations in the ATM gene. Typically, it presents in early childhood with progressive cerebellar dysfunction along with immunodeficiency and oculocutaneous telangiectasia. An increased risk of malignancy is also associated with the syndrome and, rarely, may be the presenting feature in small children. We describe a 17-year-old boy with slurred speech, mild motor delays and learning disability diagnosed with atypical A-T in the setting of T-cell acute lymphoblastic leukemia. Suspicion for A-T was raised after review of a peripheral blood karyotype demonstrating rearrangements involving chromosomes 7 and/or 14. The diagnosis was confirmed after molecular testing identified a novel homozygous missense variant in ATM (c.5585T>A; p.Leu1862His) that resulted in protein instability and abolished serine/threonine protein kinase activity. To our knowledge, this is the first report of concurrent A-T and lymphoid malignancy diagnoses in an older child or adult with only mild neurological disease. Our experience suggests that screening for the disorder should be considered in any individual with lymphoid malignancy and neurological findings, especially as radiation and certain chemotherapy protocols are contraindicated in A-T.
authors.affiliation: Clinical Genetics, Kaiser Permanente Mid-Atlantic Medical Group, Formerly Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, Rockville, MD, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Roohi
authors.affiliation: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Crowe
authors.affiliation: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Denis
authors.initials: D
authors.lastname: Loredan
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
authors.affiliation: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Mansukhani
authors.affiliation: Division of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Lenore
authors.initials: L
authors.lastname: Omesi
authors.affiliation: Division of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Levine
authors.affiliation: Institute for Genomic Medicine, Columbia University Medical Center, New York, NY, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Revah Politi
authors.affiliation: Institute for Cancer Genetics, Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, USA.|Division of Hematology-Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Zha
mesh_terms: D000293:Adolescent; D001260:Ataxia Telangiectasia / Q000150:complications* / Q000175:diagnosis*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000235:genetics*
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins