title: Novel frameshift and splice site mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) associated with hereditary sensory neuropathy type IV.
abstract: Congenital insensitivity to pain with anhidrosis or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is the first human genetic disorder implicated in the neurotrophin signal transduction pathway. HSAN IV is characterized by absence of reaction to noxious stimuli, recurrent episodes of fever, anhidrosis, self-mutilating behavior and often mental retardation. Mutations in the neurotrophic tyrosine kinase, receptor, type 1 (NTRK1) are associated with this disorder. Here we report four homozygous mutations, two frameshift (p.Gln626fsX6 and p.Gly181fsX58), one missense (p.Arg761Trp) and one splice site (c.359+5G>T) mutation in four HSAN IV patients. The splice site mutation caused skipping of exons 2 and 3 in patient's mRNA resulting in an in-frame deletion of the second leucine-rich motif. NTRK1 mutations are only rarely reported in the European population. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with HSAN IV.
authors.affiliation: Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, B-2610 Antwerpen, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Verpoorten
authors.forename: Kristl G
authors.initials: KG
authors.lastname: Claeys
authors.forename: Liesbet
authors.initials: L
authors.lastname: Deprez
authors.forename: An
authors.initials: A
authors.lastname: Jacobs
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Gerwen
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
authors.forename: Willem Frans
authors.initials: WF
authors.lastname: Arts
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
authors.forename: Kathelijn
authors.initials: K
authors.lastname: Keymolen
authors.forename: Chantal
authors.initials: C
authors.lastname: Ceuterick-de Groote
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Vincent
authors.initials: V
authors.lastname: Timmerman
authors.forename: Eva
authors.initials: E
authors.lastname: Nelis
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D020125:Mutation, Missense / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020917:Receptor, trkA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012867:Skin / Q000473:pathology / Q000648:ultrastructure
chemical_list: D022821:RNA Splice Sites; D012333:RNA, Messenger; D020917:Receptor, trkA