{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:05:55Z","timestamp":1753891555210,"version":"3.41.2"},"reference-count":14,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T00:00:00Z","timestamp":1662508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>We report a case of congenital insensitivity to pain with anhidrosis (CIPA) with a novel neurotrophic tyrosine kinase receptor type 1 (<jats:italic>NTRK1<\/jats:italic>) gene mutation. The patient suffered from recurrent corneal ulcer. A slit-lamp examination revealed ciliary hyperemia, bulbar conjunctival edema, epithelial defect, and ulcer lesion in the inferior part of the cornea, local corneal stromal edema accompanied by new vascular growth in his affected eye. In addition, the corneal sensitivity and nerve fiber density decreased significantly in both eyes. Tear film break-up time and Schirmer\u2019s I test were below lower limit. Moreover, the patient exhibited typical systemic features, including no normal response to pain stimuli, anhidrosis and self-injurious behavior. Gene sequencing revealed a compound-heterozygous mutations in <jats:italic>NTRK1<\/jats:italic> gene: a missense mutation inherited from his mother (c.1750G &amp;gt; A, P.E584K) and a new splicing mutation inherited from his father (c.2187 + 5G &amp;gt; C). After 8 weeks of medication, the corneal ulcer basically healed. This study expands the spectrum of <jats:italic>NTRK1<\/jats:italic> gene mutation associated with CIPA and provides a feasible approach for clinicians to treat patients with CIPA-related keratopathy.<\/jats:p>","DOI":"10.3389\/fmed.2022.955929","type":"journal-article","created":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T04:58:22Z","timestamp":1662526702000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Ophthalmic findings of congenital insensitivity to pain with anhidrosis with a novel neurotrophic tyrosine kinase receptor type 1 gene mutation: A case report"],"prefix":"10.3389","volume":"9","author":[{"given":"Rong","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingpeng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhensheng","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1007\/s10048-021-00668-z","article-title":"NTRK1 gene-related congenital insensitivity to pain with anhidrosis: a nationwide multicenter retrospective study.","volume":"22","author":"Echaniz-Laguna","year":"2021","journal-title":"Neurogenetics."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1177\/1744806918781140","article-title":"Novel NTRK1 mutations in Chinese patients with congenital insensitivity to pain with anhidrosis.","volume":"14","author":"Geng","year":"2018","journal-title":"Mol Pain."},{"key":"B3","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1001\/archneur.1963.00460030083008","article-title":"Congenital insensitivity to pain with anhydrosis. A unique syndrome in two male siblings.","volume":"8","author":"Swanson","year":"1963","journal-title":"Arch Neurol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/805876","article-title":"Congenital corneal anesthesia and neurotrophic keratitis: diagnosis and management.","volume":"2015","author":"Mantelli","year":"2015","journal-title":"Biomed Res Int."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-020-00764-3","article-title":"Clinical, genomics and networking analyses of a high-altitude native American Ecuadorian patient with congenital insensitivity to pain with anhidrosis: a case report.","volume":"13","author":"Lopez-Cortes","year":"2020","journal-title":"BMC Med Genomics."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.638190","article-title":"Novel gross deletion mutations in NTRK1 gene associated with congenital insensitivity to pain with anhidrosis.","volume":"9","author":"Li","year":"2021","journal-title":"Front Pediatr."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-015-0215-x","article-title":"Novel transcripts reveal a complex structure of the human TRKA gene and imply the presence of multiple protein isoforms.","volume":"16","author":"Luberg","year":"2015","journal-title":"BMC Neurosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2018.01.013","article-title":"NGF-dependent neurons and neurobiology of emotions and feelings: lessons from congenital insensitivity to pain with anhidrosis.","volume":"87","author":"Indo","year":"2018","journal-title":"Neurosci Biobehav Rev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/nrneurol.2011.227","article-title":"Mechanisms of disease in hereditary sensory and autonomic neuropathies.","volume":"8","author":"Rotthier","year":"2012","journal-title":"Nat Rev Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.medcli.2020.11.019","article-title":"Congenital insensitivity to pain with anhidrosis: a report of two unrelated Chinese families with novel mutations in NTRK1 gene.","volume":"157","author":"Li","year":"2021","journal-title":"Med Clin."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2270","DOI":"10.4103\/ijo.IJO_2101_19","article-title":"The painless eye: neurotrophic keratitis in a child suffering from hereditary sensory autonomic neuropathy type IV.","volume":"68","author":"Sethi","year":"2020","journal-title":"Indian J Ophthalmol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1097\/OPX.0000000000001255","article-title":"Case series. management of neurotrophic keratitis from familial dysautonomia.","volume":"95","author":"Scanzera","year":"2018","journal-title":"Optom Vis Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1159\/000354380","article-title":"Neurotrophic keratitis.","volume":"231","author":"Semeraro","year":"2014","journal-title":"Ophthalmologica."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1016\/j.jpeds.2012.05.038","article-title":"A rating scale for the functional assessment of patients with familial dysautonomia (Riley Day syndrome).","volume":"161","author":"Axelrod","year":"2012","journal-title":"J Pediatr."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.955929\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,7]],"date-time":"2022-09-07T04:58:25Z","timestamp":1662526705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.955929\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,7]]},"references-count":14,"alternative-id":["10.3389\/fmed.2022.955929"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.955929","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,9,7]]},"article-number":"955929"}}