Clinical and genetic characteristics of <i>PLA2G6</i>-related parkinsonism in Southwest China and a comprehensive literature review.

Abstract

Biallelic <i>PLA2G6</i> mutations are associated with early onset autosomal recessive parkinsonism, exhibiting a broad spectrum of clinical heterogeneity. To comprehensively characterise the clinical, imaging and genetic features of <i>PLA2G6</i>-related parkinsonism. We report 14 new cases of <i>PLA2G6</i>-related parkinsonism in Southwest China and conduct a systematic literature review. Among the 14 patients in our cohort, 16 <i>PLA2G6</i> variants were identified, including seven novel and nine previously reported variants. The mean age at symptom onset was 26.50±6.57 years. The most common initial presentation was parkinsonism (9/14, 64.3%), followed by gait disturbance (6/14, 42.9%) and psychiatric symptoms (1/14, 7.1%). A literature review identified 118 patients with <i>PLA2G6</i>-related parkinsonism, with a mean age at onset of 24.53±8.84 years. The most common initial clinical features included parkinsonism (61/117, 52.1%), cerebellar signs (46/85, 54.1%), cognitive impairment (65/92, 70.7%) and psychiatric symptoms (80/93, 86.0%). Subgroup analysis showed that the mean age at symptom onset was older in Chinese patients (26.65±7.08 years) compared with those of European ancestry (20.83±9.79 years) (p=0.016). Additionally, patients of European ancestry showed delayed parkinsonism 5.35±8.14 years after onset. Iron deposition was reported more frequently in patients of European ancestry (10/16, 62.5%) than that in Chinese patients (6/37, 16.2%) (p=0.0002). Our study provides new insights on the diverse clinical spectrum of <i>PLA2G6</i>-related parkinsonism, encompassing parkinsonian features, psychiatric symptoms, cognitive impairment and early levodopa-induced motor complications.