{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:07:49Z","timestamp":1787879269512,"version":"build-2784847793"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T00:00:00Z","timestamp":1614816000000},"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. Pediatr."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis, recurrent fever, and intellectual disability. CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (<jats:italic>NTRK1<\/jats:italic>). This study aims to identify pathogenic mutations underlying CIPA in two unrelated Chinese families.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> DNA was extracted from blood samples of patients and their available family members and subjected to whole exome sequencing (WES). Real-time PCR (qPCR), Gap-PCR, and Sanger sequencing were applied to verify the identified variants.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> We found novel compound gross deletion mutations [exon1-6 del (g.1-1258_10169del); exon5-7 del (g.6995_11999del)] of <jats:italic>NTRK1<\/jats:italic> (MIM 191315) gene in family 1 and the compound heterozygous mutations [c.851-33T&amp;gt;A; exon5-7 del (g.6995_11999del)] in family 2. Interestingly, we discovered the intragenic novel gross deletion [exon5-7 del (g.6995_11999del)] mediated by recombination between Alu elements.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> The present study highlights two rare gross deletion mutations in the <jats:italic>NTRK1<\/jats:italic> gene associated with CIPA in two unrelated Chinese families. The deletion of exon1-6 (g.1-1258_10169del) is thought to be the largest <jats:italic>NTRK1<\/jats:italic> deletion reported to date. Our findings expand the mutation spectrum of <jats:italic>NTRK1<\/jats:italic> mutations in the Chinese and could be useful for prenatal interventions and more precise pharmacological treatments to patients. WES conducted in our study is a convenient and useful tool for clinical diagnosis of CIPA and other associated disorders.<\/jats:p>","DOI":"10.3389\/fped.2021.638190","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T04:25:45Z","timestamp":1614831945000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Novel Gross Deletion Mutations in NTRK1 Gene Associated With Congenital Insensitivity to Pain With Anhidrosis"],"prefix":"10.3389","volume":"9","author":[{"given":"Lulu","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaofang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/ng0896-485","article-title":"Mutations in the TRKA\/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis","volume":"4","author":"Indo","year":"1996","journal-title":"Nat Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1744806918781140","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":"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":"B4","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1750-1172-2-39","article-title":"Hereditary sensory and autonomic neuropathies: types II, III, and IV","volume":"2","author":"Axelrod","year":"2007","journal-title":"Orphanet J Rare Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1385\/NMM:8:1-2:147","article-title":"Molecular genetics of hereditary sensory neuropathies","volume":"8","author":"Auer-Grumbach","year":"2006","journal-title":"Neuromol Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1111\/ijd.14048","article-title":"Hypohidrotic ectodermal dysplasia: clinical and molecular review","volume":"57","author":"Reyes-Reali","year":"2018","journal-title":"Int J Dermatol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1750-1172-3-7","article-title":"Hereditary sensory neuropathy type I","volume":"3","author":"Auer-Grumbach","year":"2008","journal-title":"Orphanet J Rare Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1001\/archneur.1963.00460030083008","article-title":"Congenital insensitivity to pain with anhydrosis. 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