Objective: To look for novel and population-specific genes for PD in 50 Indian families with Parkinson’s disease

Background: Till date, 138 mutations in PINK1 and 214 mutations in Parkin genesare known to cause Parkinson’s disease (PD). Reports from India are limited.

Methods: We performed exome sequencing in 50 families showing either autosomal dominant or autosomal recessive forms of PD to find novel genes for PD.

Results: We found three new and population-specific mutations,two in the PTEN-induced putative kinase 1 (PINK1) gene and one in parkin(PRKN) gene in a total of 3 families. The new PINK1 mutations were p.Phe385Ser missense mutation in exon 6in onefamily and a stop gain mutation p.Tyr404* in exon 6 in another family (HGVS notation and exon numbers refer to the Ensembl transcript ENST00000321556). We identified a novel stop gain mutation p.Glu367* in exon 10in the PRKN gene (HGVS notation and exon number refer to the Ensembl transcript ENST00000366898).The reported mutations have not been observed in any of the database 1000 Genomes, ExAC orgnomAD. Clinically, the PINK1 mutation carriers had disease-onset at 39 and 27 years with typical motor symptoms,including asymmetry and rest tremor and both showed excellent levodopa response that was stable for over a decade before developing motor fluctuations. Dyskinesia’s were mild and disease progression slow. Both developed depression but no other non-motor symptoms. The parkin gene mutation carriers had disease onset at 37 and 42 years. Besides the typical motor symptoms, they did not report any non-motor symptoms except depression in one. Both developed early motor fluctuations within 4 years.

Conclusions: The three-novel population-specific recessive mutations were identified in PINK1 and PRKN genes from India which have not been reported in any of the PD databases.Further studies may help understand how these variants potentially affect protein function and cause neuronal death in PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/novel-population-specific-mutationsin-pink1-and-parkin-genes-from-india/