ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000006.11) (NC_000006.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype

Haploinsufficiency phenotype comments:

Deletions and loss-of-function mutations affecting both copies of the gene PRKN (formerly, PARK2) are associated with autosomal recessive, juvenile (early onset) Parkinson disease 2. Heterozygous PRKN deletions, as well as intragenic duplications, particularly involving the 5' exons, are commonly observed in the general population and in control populations. Although reports associating hemizygosity of PRKN with various developmental phenotypes exist in the literature, there is currently insufficient evidence in support of haploinsufficiency of this gene. Additional selected literature is summarized below: PMID 21360662 Scheuerle and Wilson (2011): This report describes two patients with PARK2 intragenic CNVs. The first patient had ADHD and Aspergers phenotype with normal intelligence and a deletion of exon 1 of PARK2. The second patient had a duplication involving exon 2 and a diagnosis of Autism spectrum disorder. PMID 24188901 Roberts et al (2014): This report details the findings of CMA performed on consecutive patients referred for autism and/or learning disabilities. One patient with learning disability (1/150 cases) was reported to have a 347Kb duplication involving PARK2. Inheritance unknown. This was a partial duplication involving exons 4-6. PMID 23164820 Janick et al (2014): This is a GWAS study of CNVs among cases and controls where cases are patients with ADHD. There was a significant excess of intragenic duplications and deletions (mostly duplications) in patients versus controls. The authors concluded that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. The CNVs cluster around exon 2 of PARK2. PMID 23740672 Mariani et al. Case report of an infant with a PARK2 intragenic 314Kb duplication involving exon 2 of PARK2. The infant had trisma and severe micrognathia, was hypertonic and eye movement abnormalities. The mother carried the CNV and had a normal phenotype.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity