|Tipo di tesi||Tesi di laurea magistrale|
|Titolo||Genotype-phenotype correlation in patients with ALS: a cohort study searching for the genetic signature behind the disease spectrum|
|Titolo in inglese||Correlazione genotipo-fenotipo in pazienti con Sclerosi Laterale Amiotrofica: studio di coorte per l'identificazione della signature genetica alla base della malattia|
|Struttura||Dipartimento di Scienze Biomediche, Metaboliche e Neuroscienze|
|Corso di studi||MEDICINA E CHIRURGIA (D.M.270/04)|
|Data inizio appello||2022-07-14|
|Disponibilità||Embargo di 3 anni|
|Data di rilascio||2025-07-14|
La Sclerosi Laterale Amiotrofica (SLA) è una malattia neurodegenerativa a carattere progressivo, contraddistinta dalla degenerazione dei motoneuroni nella corteccia motoria primaria, nei tratti corticospinali, nel tronco cerebrale e nelle corna anteriori nel midollo spinale.
Genotype-phenotype correlation in patients with ALS: a cohort study searching for the genetic signature behind the disease spectrum Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, characterized by degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem, and anterior horn cells of the spinal cord. The dysfunction of both upper motor neuron (UMN) and lower motor neuron (LMN) leads to painless and progressive skeletal muscle weakness and atrophy, with spasticity that evolves to paralysis. 600 mutations in more than 40 genes have been found to be associated with ALS. Although most cases are sporadic, familial amyotrophic lateral sclerosis (fALS) accounts for about 5 to 10% of patients. In about 60%-80% of patients diagnosed with fALS a putatively pathogenic mutation can be identified, with C9Orf72, SOD1, FUS, TARBDP and ATXN2 being the most frequent. The aim of this study is to examine the frequency and burden of mutations in known ALS genes within a population-based cohort; moreover, this investigation analyses correlation between genetic signature and phenotype. A sample of 97 individuals (62 men and 35 women) was collected, then genetic tests (NGS panel analysis, C9Orf72 expansions) were performed in the selected sample. Results indicate that among 71 patients with a positive genetic test, 68 presented a positive NGS panel and 9 had C9Orf72 mutations, while 6 had both the previous tests positive. Among patients with at least one positive genetic test, age of onset is lower than in those with negative genetics; moreover, patients with both positive genetic tests showed an earlier onset than previous categories. Among patients with positive genetics, bulbar phenotype is more frequently observed. The present study provides evidence that genetic analysis could contribute to a better understanding of pathogenetic mechanisms and could become a consistent part of clinical management.