Abstract
Uniparental disomy has long been recognized as a significant cause of genetic disease
in imprinting-associated conditions. More recently, it has increasingly been implicated
as a potentially significant cause of autosomal recessive disease. Here we report
a case of a patient with a history of leukemia and αβ hepatosplenic T-cell lymphoma
who was diagnosed with ataxia telangiectasia via paired tumor-germline testing at
age 20. Germline testing detected a homozygous pathogenic variant in the ATM gene. Parental testing identified this variant only in the mother, leading to suspicion
for non-paternity or an atypical cause of autosomal recessive disease. Additional
analysis of the proband's sample identified a 54 megabase region at chr11q13.4-q25
with alleles all derived from a single parent, consistent with uniparental isodisomy
as causative of autosomal recessive ataxia telangiectasia in this case. This report
provides further evidence that uniparental isodisomy should be considered in the potential
etiology of autosomal recessive conditions, including in the setting of paired tumor-germline
testing. Confirming the method of inheritance is particularly important in cases such
as this one where being a heterozygous carrier has medical management implications
for cancer screening for relatives as well as for cascade testing and family planning
for relatives.
Keywords
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Article Info
Publication History
Published online: May 20, 2022
Accepted:
May 16,
2022
Received in revised form:
March 5,
2022
Received:
September 15,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
