An Integrated Whole-Genome Sequencing and In-House Targeted Testing Strategy Enhances Comprehensive Mutation Detection in Neurofibromatosis Type 1.

Authors

Rekha Aaron, Kushagra Agarwal, Aaron Chapla, G Paramasivam, Dharshini Sathishkumar, Lydia Mathew, Anju George, Leni George, Thomas Palocaren, Ajit Sivadasan, Maya Thomas, Sumita Danda

Published in

Annals of Indian Academy of Neurology. Aug 12, 2026. Epub Aug 12, 2026.

Abstract

Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurocutaneous syndrome that affects 1 in 2,500-3,000 births. The phenotypic hallmarks include Lisch nodules, optic nerve gliomas, café-au-lait spots, axillary freckling, and benign neurofibromas. NF1 patients carry an 8-13% lifetime risk of malignant peripheral nerve sheath tumors, the leading cause of NF1 mortality. Current genetic testing detects NF1 variants in 95-97% of cases. In this prospective cohort of 103 cases, we used targeted NF1 sequencing by next-generation sequencing, multiplex ligation-dependent probe amplification (MLPA), and whole-genome sequencing to identify causative variants. Pathogenic or likely pathogenic variants were identified by in-house targeted testing in 93% of cases; six cases had large deletions detected by MLPA, and two had variants identified by whole-genome sequencing. This is the largest genetically confirmed Indian NF1 cohort reported, expanding the known mutational spectrum and demonstrating the utility of whole-genome sequencing for unresolved cases (~2%), as well as highlighting the clinical and genetic heterogeneity of NF1.

PMID:
42616921
Bibliographic data and abstract were imported from PubMed on 20 Aug 2026.

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