Ataxia-telangiectasia (A-T), an autosomal recessive disorder characterized by progressive neurologic dysfunction, oculocutaneous telangiectasia, immunodeficiency, and cancer susceptibility, is caused by mutations in the ATM gene. A previous study of 4 A-T patients identified 2 rare homozygous missense mutations residing on the same allele of the ATM gene: c.1514T>C and c.1547T>C, which were shown to decrease ATM levels and increase T-cell acute lymphoblastic leukemia predisposition. We studied 5 patients from 2 consanguineous Bedouin families of the same tribe, presenting with A-T. Whole-exome sequencing data identified the 2 aforementioned mutations in ATM, which segregated within all family members as expected of autosomal recessive heredity. Interestingly, one individual was diagnosed with malignant peritoneal mesothelioma (MPM), an extremely rare neoplasm in pediatric patients. Here, we describe a case of a 4-month-old infant homozygous for the 2 ATM mutations, who developed MPM and died by the age of 2 years. To the best of our knowledge, this is the first case of peritoneal mesothelioma in an infant bearing ATM mutations, and one of the youngest pediatric mesotheliomas described. Thus, the risk of MPM might be considered in the follow-up of A-T patients, and ATM mutations sought in cases of early-onset MPM.
*Zussman Child Development Center, Soroka Medical Center, Faculty of Health Sciences
†The Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev and Faculty of Health Sciences
‡Department of Pathology
§Pediatric Hematology Unit
∥Genetics Institute, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel
A.M. and D.H. contributed equally.
Supported by the Legacy Heritage Bio-Medical Program of the Israel Science Foundation (grant no. 1798/16) awarded to Professor O.S.B.
The authors declare no conflict of interest.
Reprints: Ohad S. Birk, MD, PhD, Genetics Institute, Soroka Medical Center, P.O. Box 151, Beer Sheva 84101, Israel (e-mail: email@example.com).
Received November 4, 2017
Accepted July 19, 2018