title: Acute lymphoblastic leukemia in early childhood as the presenting sign of ataxia-telangiectasia variant.
abstract: Ataxia-telangiectasia (A-T), an autosomal recessive disorder is characterized by progressive neurodegeneration, immunodeficiency, sensitivity to ionizing radiation, and predisposition to cancer, especially to lymphoid malignancies. A-T variant is characterized by a milder clinical phenotype and is caused by missense or leaky splice site mutations that produce residual ataxia telangiectasia mutated (ATM) kinase activity. Lymphoid malignancy can precede the diagnosis of A-T, particularly in young children with mild neurological symptoms. We studied a consanguineous family with four A-T variant patients, three of them developed T-ALL at a young age before the diagnosis of A-T was established. ATM mutation analysis detected two new missense mutations both within exon 12: c.1514T>C and c.1547T>C. All four patients are homozygous for the two mutations, while their parents are heterozygous for the mutations. ATM protein level was low in all patients and the response to the radiomimetic agent, neocarzinostatin, was reduced. Leukemic presentation in a young age in three members of consanguineous family led to the identification of a new missense mutation in the ATM gene. The diagnosis of A-T or A-T variant should be considered in children with neurological abnormalities who develop T-ALL at a young age.
authors.affiliation: Department of Pediatric Hematology-Oncology, Safra Children's Hospital, Tel-Hashomer, Ramat-Gan, Israel. bielorab@netvision.net.il
authors.forename: Bella
authors.initials: B
authors.lastname: Bielorai
authors.forename: Tamar
authors.initials: T
authors.lastname: Fisher
authors.forename: Dalia
authors.initials: D
authors.lastname: Waldman
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Lerenthal
authors.forename: Andreea
authors.initials: A
authors.lastname: Nissenkorn
authors.forename: Tali
authors.initials: T
authors.lastname: Tohami
authors.forename: Dina
authors.initials: D
authors.lastname: Marek
authors.forename: Ninette
authors.initials: N
authors.lastname: Amariglio
authors.forename: Amos
authors.initials: A
authors.lastname: Toren
mesh_terms: D000328:Adult; D000367:Age Factors; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D001260:Ataxia Telangiectasia / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D009353:Zinostatin / Q000008:administration & dosage*
chemical_list: D000903:Antibiotics, Antineoplastic; D009353:Zinostatin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins