scholarly journals Investigation of a Novel NTRK1 Variation Causing Congenital Insensitivity to Pain With Anhidrosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Yang ◽  
Yi-Cheng Xu ◽  
Hua-Ying Hu ◽  
Ya-Zhou Li ◽  
Qian Li ◽  
...  
Keyword(s):  
Mrna Level ◽  
Sensory Neuropathy ◽  
Functional Study ◽  
Structure Stability ◽  
Compound Heterozygous ◽  
The Novel ◽  
Congenital Insensitivity ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain

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 NTRK1Arg748Trp 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.

scholarly journals A novel SCN9A splicing mutation in a compound heterozygous girl with congenital insensitivity to pain, hyposmia and hypogeusia

2018 ◽  
Vol 23 (3) ◽  
pp. 202-206 ◽  
Author(s):  
Margherita Marchi ◽  
Vincenzo Provitera ◽  
Maria Nolano ◽  
Marcello Romano ◽  
Simona Maccora ◽  
...  
Keyword(s):  
Compound Heterozygous ◽  
Splicing Mutation ◽  
Congenital Insensitivity ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain

Novel SCN9A Mutations in a Compound Heterozygous Girl with Congenital Insensitivity to Pain

2020 ◽  
Author(s):  
Bas Stunnenberg ◽  
Charlotte Haaxma ◽  
Mieke van Haelst ◽  
Maria Ponson-Wever ◽  
Eline Verberne ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Frameshift Mutation ◽  
Rare Disorder ◽  
Compound Heterozygous ◽  
Α Subunit ◽  
Voltage Gated ◽  
Congenital Insensitivity ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain ◽  
Inactivating Mutations

AbstractCongenital Insensitivity to Pain (CIP) is a rare disorder that is characterized by the inability to perceive pain. It is caused by bi-allelic inactivating mutations in the SCN9A gene, which encodes the pore-forming α-subunit of the nerve voltage-gated sodium channel (Nav1.7). Patients with CIP are unable to feel pain from noxious stimuli, including heat, but all other peripheral somatosensory modalities function normally. Often anosmia is present as an additional feature. We report a patient with CIP caused by compound heterozygous SCN9A mutations: a novel in-frame deletion of exon 7 and a novel frameshift mutation. The identification of these mutations expands the spectrum of mutations associated with CIP.

scholarly journals Novel Gross Deletion Mutations in NTRK1 Gene Associated With Congenital Insensitivity to Pain With Anhidrosis

2021 ◽  
Vol 9 ◽  
Author(s):  
Lulu Li ◽  
Chao Jia ◽  
Yue Tang ◽  
Yuanyuan Kong ◽  
Yaofang Xia ◽  
...  
Keyword(s):  
Autosomal Recessive Disorder ◽  
Recurrent Fever ◽  
Tyrosine Kinase Receptor ◽  
Compound Heterozygous ◽  
Chinese Families ◽  
Alu Elements ◽  
Deletion Mutations ◽  
Congenital Insensitivity ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain

Background: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis, recurrent fever, and intellectual disability. CIPA is mainly caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1). This study aims to identify pathogenic mutations underlying CIPA in two unrelated Chinese families.Methods: DNA was extracted from blood samples of patients and their available family members and subjected to whole exome sequencing (WES). Real-time PCR (qPCR), Gap-PCR, and Sanger sequencing were applied to verify the identified variants.Result: We found novel compound gross deletion mutations [exon1-6 del (g.1-1258_10169del); exon5-7 del (g.6995_11999del)] of NTRK1 (MIM 191315) gene in family 1 and the compound heterozygous mutations [c.851-33T>A; exon5-7 del (g.6995_11999del)] in family 2. Interestingly, we discovered the intragenic novel gross deletion [exon5-7 del (g.6995_11999del)] mediated by recombination between Alu elements.Conclusions: The present study highlights two rare gross deletion mutations in the NTRK1 gene associated with CIPA in two unrelated Chinese families. The deletion of exon1-6 (g.1-1258_10169del) is thought to be the largest NTRK1 deletion reported to date. Our findings expand the mutation spectrum of NTRK1 mutations in the Chinese and could be useful for prenatal interventions and more precise pharmacological treatments to patients. WES conducted in our study is a convenient and useful tool for clinical diagnosis of CIPA and other associated disorders.

scholarly journals Guided growth in the correction of knee deformity in patients with congenital insensitivity to pain

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Soroush Baghdadi ◽  
Sadegh Saberi ◽  
Taghi Baghdadi
Keyword(s):  
Demographic Data ◽  
Joint Destruction ◽  
Walking Ability ◽  
Guided Growth ◽  
Tertiary Referral Hospital ◽  
Common Procedure ◽  
Correction Rate ◽  
Congenital Insensitivity ◽  
Congenital Insensitivity To Pain ◽  
Insensitivity To Pain

Abstract Background Orthopedic manifestations of congenital insensitivity to pain (CIP) can be devastating if left untreated. Knee deformities are common in patients with CIP and might lead to joint destruction and loss of walking ability. The purpose of the present study was to report the results and complications of guided growth procedures around the knee in patients with CIP. Methods In a retrospective review, all patients with CIP who underwent guided growth procedures around the knee from 2009 to 2017 at a tertiary referral hospital were evaluated. Patients with secondary insensitivity to pain (e.g., syringomyelia), as well as patients with incomplete records, were excluded. Demographic data, clinical findings, correction rate, and complications were recorded. Results Ten knees in six patients fulfilled the inclusion criteria. The median age was 10 (range, 5–12), with a mean follow-up of 31 months (range, 16–56). Distal femoral tension-band hemiepiphysiodesis was the most common procedure, followed by proximal tibial hemiepiphysiodesis. The mean correction rate was 0.28°/month for femoral deformity. Staples were removed prematurely in one patient due to extrusion. No cases of infection or skin dehiscence were observed. None of the patients needed a reconstructive knee procedure during the study period. Conclusions The findings of this study suggest that guided growth procedures might have a role in the correction of knee deformities in patients with CIP. However, the correction rate is lower than that of typically developing children, patients should be closely followed to prevent complications, and stringent patient selection criteria should be followed to ensure success.

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