title: Recurrent and novel mutations in the NTRK1 gene lead to rare congenital insensitivity to pain with anhidrosis in two Chinese patients.
abstract: BACKGROUND
  Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive autonomic and sensory neuropathy. CIPA is associated with various mutations in NTRK1.
  
  
  METHODS
  Two unrelated Chinese patients presented separately with symptoms of insensitivity to pain, inability to sweat, repeated painless fractures, and Charcot arthropathy were recruited. Both of them were clinically diagnosed with CIPA. Increased serum bone resorption marker (β-CTX) levels and decreased BMD were observed in both patients. X-ray films revealed enlarged bony calli in the fracture sites, Charcot arthropathy, and bilateral lower limb osteomyelitis. Sanger sequencing demonstrated compound heterozygous mutations in NTRK1 for proband 1 (IVS7-33T>A in intron 7 and c. 2281C>T in exon 17) and for proband 2 (IVS7-33T>A in intron 7 and c.1652delA in exon 14), of which the variation in exon 14 in NTRK1 was a novel mutation.
  
  
  CONCLUSIONS
  We report the detailed phenotypes, as well as both recurrent and novel mutations in NTRK1 in 2 Chinese patients with CIPA. The genetic findings of our study expand the gene mutation spectrum of CIPA.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Song
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Lu-Jiao
authors.initials: LJ
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Xia
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Xing
authors.affiliation: Department of Orthopaedics, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address: gaopengpumch@icloud.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China. Electronic address: limeilzh@sina.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000201:enzymology* / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D020917:Receptor, trkA / Q000737:chemistry / Q000235:genetics*; D055815:Young Adult
chemical_list: D020917:Receptor, trkA
keywords: CIPA; Charcot arthropathy; NTRK1; Novel mutation; Painless fractures