The KM-parkin-DB: A Sub-set MutationView Database Specialized for PARK2 (PARKIN) Variants

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• The PARK2 gene, encoding the Parkin protein, is known to cause Autosomal Recessive Juvenile Parkinsonism (ARJP).
• Understanding the spectrum of PARK2 mutations is crucial for diagnosing and potentially treating Parkinson disease (PD).

Purpose of the Study:

• To comprehensively survey and curate literature on PARK2 gene and Parkin protein mutations in Parkinson disease patients.
• To establish an independent database (KM-parkin-DB) of curated mutation data.

Main Methods:

• Systematic literature review of articles reporting PARK2 mutations in PD patients.
• Data curation from 44 selected articles, including clinical information (ethnicity, symptoms, onset, inheritance) and mutation details (base changes, zygosity).
• Creation of the KM-parkin-DB database using curated data from the MutationView graphical database.

Main Results:

• A total of 366 cases from 39 ethnic origins were collected.
• 96 pathogenic mutations in the PARK2 gene were identified.
• PARK2 mutations were found in both ARJP and general Parkinson disease patients.
• The majority of mutations (63%) were located in the UBL and RING1 domains of the Parkin protein.
• Two prevalent mutations, DelEx3 (large deletion) and p.Arg275Trp (point mutation), were identified within these domains.

Conclusions:

• This study provides a comprehensive catalog of PARK2 mutations associated with Parkinson disease.
• The findings highlight the importance of the UBL and RING1 domains in PARK2-related Parkinsonism.
• KM-parkin-DB serves as a valuable resource for researchers investigating the genetic basis of Parkinson disease.