<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Inherited peripheral neuropathies (IPN) are a clinically and genetically heterogeneous group of disorders. The most common IPN is Charcot-Marie-Tooth (CMT) disease. Here we describe IPN clinical variability and diagnostic characteristics in the Latvian population. A total of 101 patients were enrolled in the study. Genetic testing consisted of PMP22 copy number analysis and whole-exome sequencing (WES). Clinical assessment comprised CMT Neuropathy Score version 2 (CMTNSv2), CMT Examination Score, pain, anxiety and memory/cognitive ability testing. The diagnostic yields for PMP22 copy number detection and WES were 45.8% and 77.8%, respectively. Disease severity assessment indicated high clinical heterogeneity, with CMTNSv2 scores ranging between 0 and 33. More than one-third of patients reported pain, and it was found to be significantly more common in patients with at least a mild anxiety level. From the initial development of symptoms, on average, it took more than 13 years for a diagnosis of IPN to be confirmed. This study updates the IPN genetic and clinical profile of the Latvian population and demonstrates the presence of a high level of heterogeneity. The time to diagnosis for IPN patients needs to be improved by employing multiplex ligation-dependent probe amplification initially followed by WES.</p>
</abstract>

Inherited peripheral neuropathies (IPN) are a clinically and genetically heterogeneous group of disorders. The most common IPN is Charcot-Marie-Tooth (CMT) disease. Here we describe IPN clinical variability and diagnostic characteristics in the Latvian population. A total of 101 patients were enrolled in the study. Genetic testing consisted of PMP22 copy number analysis and whole-exome sequencing (WES). Clinical assessment comprised CMT Neuropathy Score version 2 (CMTNSv2), CMT Examination Score, pain, anxiety and memory/cognitive ability testing. The diagnostic yields for PMP22 copy number detection and WES were 45.8% and 77.8%, respectively. Disease severity assessment indicated high clinical heterogeneity, with CMTNSv2 scores ranging between 0 and 33. More than one-third of patients reported pain, and it was found to be significantly more common in patients with at least a mild anxiety level. From the initial development of symptoms, on average, it took more than 13 years for a diagnosis of IPN to be confirmed. This study updates the IPN genetic and clinical profile of the Latvian population and demonstrates the presence of a high level of heterogeneity. The time to diagnosis for IPN patients needs to be improved by employing multiplex ligation-dependent probe amplification initially followed by WES.

Phenotypic Variability and Diagnostic Characteristics in Inherited Peripheral Neuropathy in Latvia

Scientific Laboratory of Molecular Genetics

Children’s Clinical University Hospital

Proceedings of the Latvian Academy of Sciences. Section B. Natural, Exact, and Applied Sciences.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Inherited peripheral neuropathies (IPN) are a clinically and genetically heterogeneous group of disorders. The most common IPN is Charcot-Marie-Tooth (CMT)...

Phenotypic Variability and Diagnostic Characteristics in Inherited Peripheral Neuropathy in Latvia

Pubblicato online: 02 giu 2022

Pagine: 232 - 238

Ricevuto: 09 ago 2021

Accettato: 26 ott 2021

DOI: https://doi.org/10.2478/prolas-2022-0035

Parole chiave
genetic, Charcot-Marie-Tooth disease, phenotype, diagnosis

© 2022 Elīna Millere et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Phenotypic Variability and Diagnostic Characteristics in Inherited Peripheral Neuropathy in Latvia

Pubblicato online: 02 giu 2022

Pagine: 232 - 238

Ricevuto: 09 ago 2021

Accettato: 26 ott 2021

DOI: https://doi.org/10.2478/prolas-2022-0035

Parole chiavegenetic, Charcot-Marie-Tooth disease, phenotype, diagnosis

© 2022 Elīna Millere et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Parole chiave
genetic, Charcot-Marie-Tooth disease, phenotype, diagnosis