{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T17:15:01Z","timestamp":1779297301955,"version":"3.51.4"},"reference-count":52,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T00:00:00Z","timestamp":1712275200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss\u2010of\u2010function mutations of the <jats:italic>NTRK1<\/jats:italic> gene, affecting the autonomic and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self\u2010mutilating behavior, and intellectual disability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1\u2009year (age range: 0.3\u20138\u2009years). Two patients exhibited self\u2010mutilation tendencies, intellectual disability, and developmental delay. Four <jats:italic>NTRK1<\/jats:italic> (NM_002529.3) mutations, c.851\u201033T&gt;A (p.?), c.2020G&gt;T (p.Asp674Tyr), c.2303C&gt;T (p.Pro768Leu), and c.574\u2010156_850+1113del (exons 5\u20107 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851\u201033T&gt;A (p.?) mutations and compound heterozygous for c.851\u201033T&gt;A (p.?) and c.2020G&gt;T (p.Asp674Tyr) mutation of <jats:italic>NTRK1<\/jats:italic>. The third patient with compound heterozygous mutations of c.2303C&gt;T (p.Pro768Leu) and c.574\u2010156_850+1113del (exons 5\u20107 del) displayed a late onset and milder clinical manifestation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2430","type":"journal-article","created":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T05:21:08Z","timestamp":1712380868000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: Case reports and a review of the literature"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2741-6554","authenticated-orcid":false,"given":"Jun Hee","family":"Cho","sequence":"first","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-237X","authenticated-orcid":false,"given":"Soojin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Medical Genetics Center, Asan Medical Center University of Ulsan College of Medicine  Seoul Republic of Korea"},{"name":"Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon Hae","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Asan Medical Center Children's Hospital University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi\u2010Sun","family":"Yum","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1518-1791","authenticated-orcid":false,"given":"Go Hun","family":"Seo","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, 3billion, Inc.  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