Tonin Rodolfo, Ramat Silvia, Rinaldi Marina, Falliano Silvia, Feo Federica, Cardona Francesca, Matassini Camilla, Mannaioni Guido, Grigioni Giulia, Caremani Luca, Govoni Alessandra, Della Bona Maria Luisa, la Marca Giancarlo, Guerrini Renzo, Morrone Amelia
Department of Neuroscience and Medical Genetics, Meyer Children's Hospital IRCCS, Florence, Italy.
Parkinson Unit, AOU Careggi, Florence, Italy.
Clin Park Relat Disord. 2025 Apr 12;12:100326. doi: 10.1016/j.prdoa.2025.100326. eCollection 2025.
heterozygous mutations in the glucocerebrosidase gene (), encoding the lysosomal enzyme β-glucocerebrosidase (GCase) are the most common genetic risk factor for Parkinson's disease (PD). To assess the frequency of variants related to PD in a cohort of Tuscany patients and to determine the link between variants and motor and non-motor clinical features in PD.
We screened GCase enzyme activity on Dried Blood Spot using tandem mass spectrometry (LC-MS/MS) and performed sequencing analysis on entire cohort of PD patients by Next Generation Sequencing (NGS) technology. Variants were confirmed with Sanger method.
among the 252 PD patients, we detected reduced GCase activity (≤5 μmol/h/L) in 78 (31%). NGS analysis identified 22 carriers of variants (8.7%) in whom 14 carried common variants currently known to be related to PD (Leu444Pro, Asn370Ser, Glu326Lys, Thr369Met and Asp409His). PD patients who were heterozygous carriers of pathogenic variants presented with earlier onset of PD, faster disease progression and a more frequent non-motor symptoms compared to the remaining PD patients without mutations.
8.7% of the 252 PD patients carried variants at a heterozygous level, and their clinical presentation and progression were more severe compared to other patients within our cohort.
编码溶酶体酶β-葡萄糖脑苷脂酶（GCase）的葡萄糖脑苷脂酶基因（）中的杂合突变是帕金森病（PD）最常见的遗传风险因素。旨在评估一组托斯卡纳患者中与PD相关的变体频率，并确定这些变体与PD患者运动和非运动临床特征之间的联系。
我们使用串联质谱法（LC-MS/MS）在干血斑上筛选GCase酶活性，并通过下一代测序（NGS）技术对整个PD患者队列进行测序分析。用桑格法确认变体。
在252例PD患者中，我们检测到78例（31%）GCase活性降低（≤5μmol/h/L）。NGS分析确定了22例变体携带者（8.7%），其中14例携带目前已知与PD相关的常见变体（Leu444Pro、Asn370Ser、Glu326Lys、Thr369Met和Asp409His）。与其余无突变的PD患者相比，携带致病性变体杂合子的PD患者PD发病更早、疾病进展更快且非运动症状更频繁。
252例PD患者中有8.7%为杂合水平的变体携带者，与我们队列中的其他患者相比，他们的临床表现和疾病进展更为严重。
