Neurol. praxi. 2024;25(4):289-294 | DOI: 10.36290/neu.2024.044

Analysis of associated genes with neurodegenerative diseases: practical experience of neurodegenerative centers in FTN

RNDr. Eva Parobková, Ph.D.¹, MUDr. Petr Šuhaj¹, Ing. Hana Šulcová¹, prof. MUDr. Radoslav Matěj, Ph.D.^{1, 2, 3}

¹ Ústav patologie a molekulární medicíny 3. LF UK a FTN, Praha

² Ústav patologie, Ústav patologie 3. LF UK a FNKV, Praha

³ Ústav patologie 1. LF UK a VFN, Praha

In 2009, next-generation sequencing (NGS) proved to be a very powerful tool in identifying variants associated with many neurodegenerative diseases. Whole-exome sequencing and whole-genome sequencing are effective for identifying variants in new or unexpected genes responsible for inherited diseases, while targeted sequen­cing is useful in detecting variants in previously known disease-associated genes. The wealth of genetic data provided by NGS has had a significant impact on clinical diagnoses while contributing to these discoveries of the molecular mechanisms underlying disease. However, eluciding the roles of the found variants identified by NGS, and especially the variants of unclear significance (VUS), is challenging and the cooperation of a geneticist, a neurologist and a neuropathologist is absolutely key. The establishment of consensus guidelines and the development of public genomic/phenotypic databases are therefore essential to facilitate data sharing and validation. In this review article, we will provide a systematic overview of the most frequent mutations in neuropathologically diagnosed patients with neurodegenerative diseases and summarize genetic diagnostic techniques and the importance of bioinformatics in the interpretation of neurodegenerative disease results.

Keywords: neurodegenerative disease, neurogenetics, next generation sequencing, targeted sequencing, whole exome sequencing.

Received: February 26, 2024; Revised: June 10, 2024; Accepted: June 10, 2024; Prepublished online: June 10, 2024; Published: September 10, 2024  Show citation