Compound heterozygous mutations in PARK2 causing early-onset Parkinson disease: A case report

Parkinson disease (PD) is a complex neurodegenerative movement disorder characterized by resting tremor, muscular rigidity, bradykinesia, and so on. Genetics has been regarded as an important role in the development of PD. PARK2, an autosomal recessive gene, is the most common one referring to early-onset Parkinson disease (EOPD). Strangely, only a single heterozygous mutation in PARK2 was found in a small minority of patients with PD, which has been reported quite rarely and is difficult to explain.

We described a case of 36-year-old male patient, complaining of progressive tremor for 10 years. He 1st presented uncontrolled resting tremor of his left arm. Besides, he also had trouble in completing fine motor tasks such as writing and buttoning. Six years later, tremor of the ipsilateral leg gradually occurred. On neurologic examinations, pronounced parkinsonian symptoms were noted, including resting tremor, body bradykinesia, and hypomimia. The positron emission tomography-computed tomography showed the distribution of dopamine transporter in both putamens decreased obviously. No family history was indentified. He came to hospital because his disease aggravated in the past 4 months.

This patient was diagnosed with PD according to the movement disorder society clinical diagnostic criteria for PD.

With regard to the sequencing of this patient, a heterozygous point mutation of G403C in PARK2 was detected, which was inherited from his unaffected mother, leading to an amino acid alternation of glycine to arginine. Furthermore, deletion mutation of exon 6 in PARK2 was also found in this patient, which was inherited from his normal father. He accepted madopar and benzhexol and showed stable efficacy. To our knowledge, it is the 1st case report to explain the synergistic action of both heterozygous pathogenic point mutation in PARK2 and deletion mutation of exon 6 leading to EOPD.

Compound heterozygous mutations in PARK2 with point mutation of G403C and deletion mutation of exon 6 might contribute to the development of EOPD.