title: Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.
abstract: Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.
authors.affiliation: Department of Pediatrics, Division of Genetics, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.forename: Fatih
authors.initials: F
authors.lastname: Bayrakli
authors.forename: Michael L
authors.initials: ML
authors.lastname: DiLuna
authors.forename: Kaya
authors.initials: K
authors.lastname: Bilguvar
authors.forename: Yasar
authors.initials: Y
authors.lastname: Bayri
authors.forename: Cengiz
authors.initials: C
authors.lastname: Yalcinkaya
authors.forename: Aysegul
authors.initials: A
authors.lastname: Bursali
authors.forename: Elif
authors.initials: E
authors.lastname: Ozdamar
authors.forename: Baris
authors.initials: B
authors.lastname: Korkmaz
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Mason
authors.forename: Ali K
authors.initials: AK
authors.lastname: Ozturk
authors.forename: Richard P
authors.initials: RP
authors.lastname: Lifton
authors.forename: Matthew W
authors.initials: MW
authors.lastname: State
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D006239:Haplotypes; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D020917:Receptor, trkA / Q000235:genetics*; D014421:Turkey
chemical_list: D020917:Receptor, trkA