title: Novel NTRK1 Frameshift Mutation in Congenital Insensitivity to Pain With Anhidrosis.
abstract: Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder. It has been reported that the defect in the NTRK1 gene encoding tropomyosin-related kinase A (TrkA) can cause congenital insensitivity to pain with anhidrosis. Nerve growth factor (NGF), the product of NGFB, mediates biological effects by binding to and activating tropomyosin-related kinase A. In addition, necdin (encoded by NDN) is also essential in nerve growth factor-tropomyosin-related kinase A pathway. We performed mutation analysis in NTRK1, NGFB, and NDN genes in a Chinese Han 17-year-old female patient with congenital insensitivity to pain with anhidrosis and her healthy family members. As a result, the patient was found to have a novel insertion in exon 7 (c.727insT) of NTRK1, which causes premature termination, and a single nucleotide polymorphism (rs2192206 G>A) in NDN. Our findings imply that the genetic variations of the nerve growth factor-tropomyosin-related kinase A pathway play an important role in congenital insensitivity to pain with anhidrosis.
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Ming
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Bioinformatics Resource Center, Biotechnology Center, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Pavelec
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Guixing
authors.initials: G
authors.lastname: Qiu
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Pediatrics, Division of Genetics and Metabolism, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Philip
authors.initials: P
authors.lastname: Giampietro
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P. R. China orthoscience@126.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D002681:China; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D010375:Pedigree; D020917:Receptor, trkA / Q000235:genetics*
chemical_list: D020917:Receptor, trkA
keywords: Necdin (NDN); congenital insensitivity to pain with anhidrosis; nerve growth factor beta (NGFB); neurotrophic tyrosine kinase receptor 1 (NTRK1)