# Next Generation Sequencing Analysis in Patients Affected by Parkinson’s Disease and Correlation Between Genotype and Phenotype in Selected Clinical Cases

## TL;DR

This study uses next-generation sequencing to analyze genetic mutations in early-onset Parkinson’s disease patients and links these mutations to specific clinical features.

## Contribution

The study validates an 8-gene NGS panel for diagnosing EOPD and correlates specific mutations with clinical phenotypes.

## Key findings

- Six patients carried likely pathogenic mutations in heterozygosity, with one having mutations in association and another with a complex genetic background.
- The p.Cys282Tyr mutation in HFE was significantly decreased in the dominant model and allele contrast comparison.
- One patient with a C9ORF72 allele containing 10 repeats was identified and clinically described.

## Abstract

Parkinson’s Disease (PD) is the most frequent movement disorder and is second only to Alzheimer’s Disease as the most frequent neurodegenerative pathology. Early onset Parkinson’s disease (EOPD) is less common and may be characterized by genetic predisposition. NGS testing might be useful in the diagnostic assessment of these patients. A panel of eight genes (SNCA, PRKN, PINK1, DJ1, LRRK2, FBXO7, GBA1 and HFE) was validated and used as a diagnostic tool. A total of 38 in sequence EOPD patients of the Parkinson’s Disease Unit of our Hospital Institution were tested. In addition, the number of the hexanucleotide repeats of the C9ORF72 gene and the frequency of main HFE mutations were evaluated. Six patients were carriers of likely pathogenic mutations in heterozygosity in the analyzed genes, one of them presented mutations in association and another had a complex genetic background. Their clinical symptoms were correlated with their genotypes. In the cohort of patients, only the p.Cys282Tyr of HFE was significantly decreased in the dominant model and allele contrast comparison. Only one patient with one allele of C9ORF72 containing 10 repeats was identified and clinically described. The clinical signs of sporadic and monogenic PD are often very similar; for this reason, it is fundamental to correlate genotypes and phenotypes, as we tried to describe here, to better classify PD patients with the aim to deepen our knowledge in the molecular mechanisms involved and collaborate in reaching a personalized management and treatment.