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Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis
Background: Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive sensory neuropathy, was caused mainly by biallelic mutations in the NTRK1 gene. The pathogenesis of CIPA still needs further elucidation. Methods: Here, we recruited a CIPA case and introduced whole-exome...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686761/ https://www.ncbi.nlm.nih.gov/pubmed/34938316 http://dx.doi.org/10.3389/fgene.2021.763467 |
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author | Yang, Kai Xu, Yi-Cheng Hu, Hua-Ying Li, Ya-Zhou Li, Qian Luan, Ying-Yi Liu, Yan Sun, Yong-Qing Feng, Zhan-Ke Yan, You-Sheng Yin, Cheng-Hong |
author_facet | Yang, Kai Xu, Yi-Cheng Hu, Hua-Ying Li, Ya-Zhou Li, Qian Luan, Ying-Yi Liu, Yan Sun, Yong-Qing Feng, Zhan-Ke Yan, You-Sheng Yin, Cheng-Hong |
author_sort | Yang, Kai |
collection | PubMed |
description | Background: Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive sensory neuropathy, was caused mainly by biallelic mutations in the NTRK1 gene. The pathogenesis of CIPA still needs further elucidation. Methods: Here, we recruited a CIPA case and introduced whole-exome sequencing (WES) to identify the causative variation. Subsequently, an in silico molecular dynamic (MD) analysis was performed to explore the intramolecular impact of the novel missense variant. Meanwhile, in vitro functional study on the novel variant from a metabolomic perspective was conducted via the liquid chromatography–mass spectrometry (LC-MS) approach, of which the result was verified by quantitative real-time PCR (qRT-PCR). Results: A novel compound heterozygous variation in NTRK1 gene was detected, consisting of the c.851–33T > A and c.2242C > T (p.Arg748Trp) variants. MD result suggested that p.Arg748Trp could affect the intramolecular structure stability. The results of the LC-MS and metabolic pathway clustering indicated that the NTRK1(Arg748Trp) variant would significantly affect the purine metabolism in vitro. Further analysis showed that it induced the elevation of NT5C2 mRNA level. Conclusion: The findings in this study extended the variation spectrum of NTRK1, provided evidence for counseling to the affected family, and offered potential clues and biomarkers to the pathogenesis of CIPA. |
format | Online Article Text |
id | pubmed-8686761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-86867612021-12-21 Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis Yang, Kai Xu, Yi-Cheng Hu, Hua-Ying Li, Ya-Zhou Li, Qian Luan, Ying-Yi Liu, Yan Sun, Yong-Qing Feng, Zhan-Ke Yan, You-Sheng Yin, Cheng-Hong Front Genet Genetics Background: Congenital insensitivity to pain with anhidrosis (CIPA), a rare autosomal recessive sensory neuropathy, was caused mainly by biallelic mutations in the NTRK1 gene. The pathogenesis of CIPA still needs further elucidation. Methods: Here, we recruited a CIPA case and introduced whole-exome sequencing (WES) to identify the causative variation. Subsequently, an in silico molecular dynamic (MD) analysis was performed to explore the intramolecular impact of the novel missense variant. Meanwhile, in vitro functional study on the novel variant from a metabolomic perspective was conducted via the liquid chromatography–mass spectrometry (LC-MS) approach, of which the result was verified by quantitative real-time PCR (qRT-PCR). Results: A novel compound heterozygous variation in NTRK1 gene was detected, consisting of the c.851–33T > A and c.2242C > T (p.Arg748Trp) variants. MD result suggested that p.Arg748Trp could affect the intramolecular structure stability. The results of the LC-MS and metabolic pathway clustering indicated that the NTRK1(Arg748Trp) variant would significantly affect the purine metabolism in vitro. Further analysis showed that it induced the elevation of NT5C2 mRNA level. Conclusion: The findings in this study extended the variation spectrum of NTRK1, provided evidence for counseling to the affected family, and offered potential clues and biomarkers to the pathogenesis of CIPA. Frontiers Media S.A. 2021-12-06 /pmc/articles/PMC8686761/ /pubmed/34938316 http://dx.doi.org/10.3389/fgene.2021.763467 Text en Copyright © 2021 Yang, Xu, Hu, Li, Li, Luan, Liu, Sun, Feng, Yan and Yin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Yang, Kai Xu, Yi-Cheng Hu, Hua-Ying Li, Ya-Zhou Li, Qian Luan, Ying-Yi Liu, Yan Sun, Yong-Qing Feng, Zhan-Ke Yan, You-Sheng Yin, Cheng-Hong Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title | Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title_full | Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title_fullStr | Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title_full_unstemmed | Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title_short | Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis |
title_sort | investigation of a novel ntrk1 variation causing congenital insensitivity to pain with anhidrosis |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686761/ https://www.ncbi.nlm.nih.gov/pubmed/34938316 http://dx.doi.org/10.3389/fgene.2021.763467 |
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