TY - JOUR
T1 - Acute lymphoblastic leukemia in early childhood as the presenting sign of ataxia-telangiectasia variant
AU - Bielorai, Bella
AU - Fisher, Tamar
AU - Waldman, Dalia
AU - Lerenthal, Yaniv
AU - Nissenkorn, Andreea
AU - Tohami, Tali
AU - Marek, Dina
AU - Amariglio, Ninette
AU - Toren, Amos
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - Ataxia-telangiectasia variant
KW - Leukemia
KW - Mutation analysis
UR - http://www.scopus.com/inward/record.url?scp=84881504493&partnerID=8YFLogxK
U2 - 10.3109/08880018.2013.777949
DO - 10.3109/08880018.2013.777949
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C2 - 23509889
AN - SCOPUS:84881504493
SN - 0888-0018
VL - 30
SP - 574
EP - 582
JO - Pediatric Hematology and Oncology
JF - Pediatric Hematology and Oncology
IS - 6
ER -