{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:15Z","timestamp":1792417395353,"version":"4.4.0"},"reference-count":14,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Neurofibromatosis type 1 (NF1) is a common autosomal dominant neurocutaneous syndrome that affects 1 in 2,500\u20133,000 births. The phenotypic hallmarks include Lisch nodules, optic nerve gliomas, caf\u00e9-au-lait spots, axillary freckling, and benign neurofibromas. NF1 patients carry an 8\u201313% lifetime risk of malignant peripheral nerve sheath tumors, the leading cause of NF1 mortality. Current genetic testing detects\n                    <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n                    variants in 95\u201397% of cases. In this prospective cohort of 103 cases, we used targeted\n                    <jats:italic toggle=\"yes\">NF1<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.4103\/aian.aian_172_26","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:00:10Z","timestamp":1786593610000},"page":"840-844","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["An Integrated Whole-Genome Sequencing and In-House Targeted Testing Strategy Enhances Comprehensive Mutation Detection in Neurofibromatosis Type 1"],"prefix":"10.4103","volume":"29","author":[{"given":"Rekha","family":"Aaron","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kushagra","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Chapla","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Paramasivam","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dharshini","family":"Sathishkumar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"George","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leni","family":"George","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Leprosy, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Palocaren","sequence":"additional","affiliation":[{"name":"Department of Paediatric Orthopedics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajit","family":"Sivadasan","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Christian Medical College, Vellore, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"R1-20261019","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1542\/peds.2007-3204","article-title":"Neurofibromatosis type 1 revisited","volume":"123","author":"Williams","year":"2009","journal-title":"Pediatrics"},{"key":"R2-20261019","first-page":"83","article-title":"Clinical outcomes of congenital pseudoarthrosis of tibia treatment: Long term study experience from our tertiary referral center","volume":"14","author":"Shareef","year":"2024","journal-title":"Int J Pharm Biol Sci"},{"issue":"(7 Suppl 1)","key":"R3-20261019","first-page":"S91","article-title":"Genotype-phenotype correlations in neurofibromatosis and their potential clinical use","volume":"97","author":"Bettegowda","year":"2021","journal-title":"Neurology"},{"key":"R4-20261019","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.4103\/ni.ni_744_22","article-title":"Clinical and molecular profile of neurofibromatosis type 1 patients using revised diagnostic criteria - A retrospective cohort study","volume":"72","author":"Rekha","year":"2024","journal-title":"Neurol India"},{"key":"R5-20261019","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jocn.2018.04.006","article-title":"Clinical characteristics and NF1 gene mutation analysis of three successive generations in three different Indian families with neurofibromatosis type 1 and peripheral nerve sheath tumours","volume":"53","author":"Prasad","year":"2018","journal-title":"J Clin Neurosci"},{"key":"R6-20261019","doi-asserted-by":"crossref","first-page":"7852","DOI":"10.1038\/s41598-023-34941-y","article-title":"Cost-effective whole exome sequencing discovers pathogenic variant causing neurofibromatosis type 1 in a family from Jammu and Kashmir, India","volume":"13","author":"Spolia","year":"2023","journal-title":"Sci Rep"},{"key":"R7-20261019","doi-asserted-by":"crossref","first-page":"e23685","DOI":"10.1016\/j.heliyon.2023.e23685","article-title":"Neurofibromatosis type 1: Clinical characteristics and mutation spectrum in a North Indian cohort","volume":"10","author":"Srivastava","year":"2024","journal-title":"Heliyon"},{"key":"R8-20261019","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1111\/cen.12541","article-title":"Maturity onset diabetes of the young in India - A distinctive mutation pattern identified through targeted next-generation sequencing","volume":"82","author":"Chapla","year":"2015","journal-title":"Clin Endocrinol (Oxf)"},{"key":"R9-20261019","doi-asserted-by":"crossref","first-page":"E173","DOI":"10.1002\/humu.20826","article-title":"Nature and mRNA effect of 282 different NF1 point mutations: Focus on splicing alterations","volume":"29","author":"Pros","year":"2008","journal-title":"Hum Mutat"},{"key":"R10-20261019","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1912735","article-title":"Selumetinib in children with inoperable plexiform neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N Engl J Med"},{"key":"R11-20261019","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1002\/ajmga.70073","article-title":"Phenotypic spectrum of neurofibromatosis type 1 patients in India and low prevalence of microdeletions in NF1 gene","volume":"200","author":"Kaur","year":"2026","journal-title":"Am J Med Genet A"},{"key":"R12-20261019","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ajhg.2017.12.001","article-title":"Genotype-phenotype correlation in NF1: Evidence for a more severe phenotype associated with missense mutations affecting NF1 codons 844-848","volume":"102","author":"Koczkowska","year":"2018","journal-title":"Am J Hum Genet"},{"key":"R13-20261019","doi-asserted-by":"crossref","first-page":"e16026","DOI":"10.7717\/peerj.16026","article-title":"DEVOUR: Deleterious variants on uncovered regions in whole-exome sequencing","volume":"11","author":"T\u00fcrk","year":"2023","journal-title":"PeerJ"},{"key":"R14-20261019","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12920-024-01795-w","article-title":"Whole genome sequencing in clinical practice","volume":"17","author":"Bagger","year":"2024","journal-title":"BMC Med Genomics"}],"container-title":["Annals of Indian Academy of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_172_26","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:02:02Z","timestamp":1792414922000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/aian.aian_172_26"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":14,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.4103\/aian.aian_172_26","relation":{},"ISSN":["0972-2327","1998-3549"],"issn-type":[{"value":"0972-2327","type":"print"},{"value":"1998-3549","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]},"assertion":[{"value":"2026-02-11","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}