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Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population

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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.

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Acknowledgments

Funding for this study came from the Program on Neurogenetics at the Yale University School of Medicine (MG, MWS). RPL is a Howard Hughes Medical Institute investigator. We are greatly indebted to the patients for their participation in this study.

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The authors report no conflicts of interest or competing interests.

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Correspondence to Murat Gunel.

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Beyhan Tüysüz and Fatih Bayrakli contributed equally to this work.

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Tüysüz, B., Bayrakli, F., DiLuna, M.L. et al. Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population. Neurogenetics 9, 119–125 (2008). https://doi.org/10.1007/s10048-008-0121-9

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  • DOI: https://doi.org/10.1007/s10048-008-0121-9

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