Acute lymphoblastic leukemia in early childhood as the presenting sign of ataxia-telangiectasia variant

Bella Bielorai, Tamar Fisher, Dalia Waldman, Yaniv Lerenthal, Andreea Nissenkorn, Tali Tohami, Dina Marek, Ninette Amariglio, Amos Toren

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)574-582
Number of pages9
JournalPediatric Hematology and Oncology
Volume30
Issue number6
DOIs
StatePublished - Sep 2013
Externally publishedYes

Keywords

  • Ataxia-telangiectasia variant
  • Leukemia
  • Mutation analysis

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