Dataset Information

Gene Distribution in Pediatric-Onset Inherited Peripheral Neuropathy: A Single Tertiary Center in Thailand.

ABSTRACT:

Background

Inherited peripheral neuropathy presents a diagnostic and therapeutic challenge due to its association with mutations in over 100 genes. This condition leads to long-term disability and poses a substantial healthcare burden on society.

Objective

This study aimed to investigate the distribution of genes and establish the genotype-phenotype correlations, focusing on pediatric-onset cases.

Methods

Exome sequencing and other analytical techniques were employed to identify pathogenic variants, including duplication analysis of the PMP22 gene. Each patient underwent physical examination and electrophysiological studies. Genotypes were correlated with phenotypic features, such as age at disease onset and ulnar motor nerve conduction velocity.

Results

We identified 35 patients with pediatric-onset inherited peripheral neuropathy. Pathogenic or likely pathogenic variants were confirmed in 24 out of 35 (68.6%) patients, with 4 of these variants being novel. A confirmed molecular diagnosis was achieved in 90.9% (10/11) of patients with demyelinating Charcot-Marie-Tooth disease (CMT) and 56.3% (9/16) of patients with axonal CMT. Among patients with infantile-onset CMT (≤2 years), the most common causative genes were MFN2 and NEFL, while GDAP1 and MFN2 were frequent causes among patients with childhood- or adolescent-onset CMT (3-9 years).

Conclusions

The MFN2 gene was the most commonly implicated gene, and the axonal type was predominant in this cohort of Thai patients with pediatric-onset inherited peripheral neuropathy.

SUBMITTER: Kulsirichawaroj P

PROVIDER: S-EPMC10789325 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Gene Distribution in Pediatric-Onset Inherited Peripheral Neuropathy: A Single Tertiary Center in Thailand.

Kulsirichawaroj Pimchanok P Suksangkharn Yanin Y Nam Da Eun DE Pho-Iam Theeraphong T Limwongse Chanin C Chung Ki Wha KW Sanmaneechai Oranee O Zuchner Stephan L SL Choi Byung-Ok BO

Journal of neuromuscular diseases 20240101 1

<h4>Background</h4>Inherited peripheral neuropathy presents a diagnostic and therapeutic challenge due to its association with mutations in over 100 genes. This condition leads to long-term disability and poses a substantial healthcare burden on society.<h4>Objective</h4>This study aimed to investigate the distribution of genes and establish the genotype-phenotype correlations, focusing on pediatric-onset cases.<h4>Methods</h4>Exome sequencing and other analytical techniques were employed to ide ...[more]

PMID: 37927275

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Project description:Inherited peripheral neuropathies (IPNs) are a group of related diseases primarily affecting the peripheral motor and sensory neurons. They include the hereditary sensory neuropathies (HSN), hereditary motor neuropathies (HMN), and Charcot-Marie-Tooth disease (CMT). Using whole-exome sequencing (WES) to achieve a genetic diagnosis is particularly suited to IPNs, where over 80 genes are involved with weak genotype-phenotype correlations beyond the most common genes. We performed WES for 110 index patients with IPN where the genetic cause was undetermined after previous screening for mutations in common genes selected by phenotype and mode of inheritance. We identified 41 missense sequence variants in the known IPN genes in our cohort of 110 index patients. Nine variants (8%), identified in the genes MFN2, GJB1, BSCL2, and SETX, are previously reported mutations and considered to be pathogenic in these families. Twelve novel variants (11%) in the genes NEFL, TRPV4, KIF1B, BICD2, and SETX are implicated in the disease but require further evidence of pathogenicity. The remaining 20 variants were confirmed as polymorphisms (not causing the disease) and are detailed here to help interpret sequence variants identified in other family studies. Validation using segregation, normal controls, and bioinformatics tools was valuable as supporting evidence for sequence variants implicated in disease. In addition, we identified one SETX sequence variant (c.7640T>C), previously reported as a putative mutation, which we have confirmed as a nonpathogenic rare polymorphism. This study highlights the advantage of using WES for genetic diagnosis in highly heterogeneous diseases such as IPNs and has been particularly powerful in this cohort where genetic diagnosis could not be achieved due to phenotype and mode of inheritance not being previously obvious. However, first tier testing for common genes in clinically well-defined cases remains important and will account for most positive results.

Project description:Introduction/objectiveExtubation failure increases morbidity and mortality in pediatric cardiac patients, a unique population including those with congenital heart disease or acquired heart disease. This study aimed to evaluate the predictive factors of extubation failure in pediatric cardiac patients and to determine the association between extubation failure and clinical outcomes.MethodsWe conducted a retrospective study in the pediatric cardiac intensive care unit (PCICU) of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, from July 2016 to June 2021. Extubation failure was defined as the re-insertion of the endotracheal tube within 48 hours after extubation. Multivariable log-binomial regression with generalized estimating equations (GEE) was performed to explore the predictive factors associated with extubation failure.ResultsWe collected 318 extubation events from 246 patients. Of these, 35 (11%) events were extubation failures. In physiologic cyanosis, the extubation failure group had significantly higher SpO2 than the extubation success group (P < 0.001). The predictive factors associated with extubation failure included a history of pneumonia before extubation (RR 3.09, 95% CI 1.54-6.23, P = 0.002), stridor after extubation (RR 2.57, 95% CI 1.44-4.56, P = 0.001), history of re-intubation (RR 2.24, 95% CI 1.21-4.12, P = 0.009), and palliative surgery (RR 1.87, 95% CI 1.02-3.43, P = 0.043).ConclusionExtubation failure was identified in 11% of extubation attempts in pediatric cardiac patients. The extubation failure was associated with a longer duration of PCICU stay but not with mortality. Patients with a history of pneumonia before extubation, history of re-intubation, post-operative palliative surgery, and post-extubation stridor should receive careful consideration before extubation and close monitoring afterward. Additionally, patients with physiologic cyanosis may require balanced circulation via regulated SpO2.

Dataset Information

Gene Distribution in Pediatric-Onset Inherited Peripheral Neuropathy: A Single Tertiary Center in Thailand.

Background

Objective

Methods

Results

Conclusions

Publications

Gene Distribution in Pediatric-Onset Inherited Peripheral Neuropathy: A Single Tertiary Center in Thailand.

Similar Datasets

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