Heterogeneous Phenotype in a Family With Compound Heterozygous Parkin Gene Mutations

Abstract

Background: Mutations in the parkin gene (PRKN) cause autosomal recessive early-onset Parkinson disease (EOPD). Objective: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. Design: Twenty members belonging to 3 generations of the EOPD family with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequencing, semiquantitative polymerase chain reaction, real-time quantitative polymerase chain reaction, and reversetranscriptase polymerase chain reaction analyses were performed to identify the PRKN mutation. Results: Compound heterozygous mutations (T240M and EX 5_6 del) in the PRKN gene were identified in 4 patients with early onset (at ages 30-38 years). Although heterozygous T240M and homozygous EX 5_6 del mutations in the PRKN gene have been previously described, this is, to our knowledge, the first report of these

A homozygous parkin p.G284R mutation in a Chinese family with autosomal recessive juvenile parkinsonism

“…It may be due to relatively young age and/or incomplete penetrance. Though heterozygous carriers of parkin mutations have been reported to have minor motor signs or present with late-onset parkinsonism [27], two elder heterozygous c.850G>C carriers (I:1, aged 56 years and I:2, aged 51 years) are free from PD, consistent with a loss-of-function mechanism of the parkin gene and findings from our previous studies [28][29][30]. Heterozygous parkin mutations were reported in only a few patients and may be caused by the second pathogenic mutation escaping detection or digenic inheritance [31].…”

Are Parkinson disease patients protected from some but not all cancers?

“…Mutations in parkin, located at 6q25.2-6q27 (PARK2, OMIM 602544), 42 are the most common cause of inherited PD accounting for up to 49% of familial recessive early-onset PD cases. [43][44][45] Parkin mutations have been also implicated in tumorigenesis, a multi-step process resulting from genetic alterations that drive the progressive transformation of normal cells into malignant derivatives. 46 Tumor suppressor genes (TSGs) are defined as genetic elements whose loss or mutational inactivation allows cells to acquire a neoplastic phenotype.…”

Mutation analysis of sporadic early-onset Alzheimer's disease using the NeuroX array

“…Variant p.T240M has been seen in EOPD as a compound heterozygote with various exon deletions or duplications (Amboni et al, 2009; Deng et al, 2006; Periquet et al, 2003; Sironi et al, 2008), it has also been seen as a homozygote (Madegowda et al, 2005) and a heterozygote (Camargos et al, 2009). A compound heterozygote with an exon deletion has also been seen in 1 healthy individual (Deng et al, 2006).…”