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Comment & Response
September 26, 2019

Missed Heterozygous Deletion in Study of Next-Generation Sequencing for Molecular Diagnosis in Patients With Infantile Nystagmus Syndrome

Author Affiliations
  • 1Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
  • 2Department of Ophthalmology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
JAMA Ophthalmol. 2019;137(12):1465-1466. doi:10.1001/jamaophthalmol.2019.3755

To the Editor In our article “Accuracy of Next-Generation Sequencing for Molecular Diagnosis in Patients With Infantile Nystagmus Syndrome,”1 we originally reported that patient 8 had a homozygous mutation (c.709C>T) in NMNAT1. The patient’s father was a heterozygous carrier for the c.709C>T mutation, but the mother was not. We suspected that this could be from uniparental disomy or maternal mosaicism. After further analysis using our customized algorithm to detect copy number variation, we noted that we missed a heterozygous deletion of exons 4 and 5 (Figure). Because the c.709C>T mutation was located in the deleted region, we could confirm the pseudohomozygosity and conclude that the patient had compound heterozygosity for hemizygous c.709C>T and heterozygous deletion of exons 4 and 5. The deletion of exons 4 and 5 in NMNAT1 was inherited from the mother.

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