Objective: To identify PARKIN mutations in PD patients with familial history (FPD) and early onset PD patients with no family history (EOPD; ≤50 years) and to establish genotype-phenotype correlations. FPD patients were further classified as early onset (FEOPD; ≤50 years) and late onset (FLOPD; >50 years) patients.

Background: Mutations in PARKIN(PARK2), are commonly encountered in familial and early onset Parkinson’s disease (PD). Certain clinical features including focal dystonia, early instability, early dyskinesia and psychosis are typical for PD patients with PARKIN mutations.1

Methods: The study was conducted at department of Neurology, Govind Ballabh Pant Institute of Postgraduate Medical Education and Research, New Delhi, and department of Genetics, University of Delhi South Campus, New Delhi. The diagnosis of PD was made based on “UK Parkinson’s disease society brain bank clinical diagnostic criteria”.2 A total of 97 patients including 45 FPD (FEOPD: 23; FLOPD: 22) and 52 EOPD patients were screened for mutations in all the12 exons of PARKIN by PCR- Sanger sequencing.

Results: A total of 25 (25.77%) patients (FEOPD:6, FLOPD:7, and EOPD:12) showed PARKIN mutations and of these nine patients showed mutations in exon 2 that included the first ever homozygous truncating mutation (Arg33Ter) in a EOPD patient. In remaining patients, mostly heterozygous mutations were observed in exon 3 (n=1 : Ala82Val); exon 4 (n=5 : Ser167Asn; with one homozygous mutation); exon 6 (n=1 : Ala230Val; n=2: Thr240Met); exon 7 (n=3: Leu272Leu; n=1: Arg275Trp; n=1: Asp280Asn); exon 9 (n=3: Arg334Cys; n=1: Ala339Ala) and exon 11 (n=2: Arg402Cys). Our cohort with PARKIN mutations showed three new phenotypes namely excessive sweating (n=1), tingling sensations in extremity (n=1) and hand stereotypy (n=1) at onset of disease. Two patients had severe retropulsion which reversed quickly with levodopa/carbidopa.

Conclusions: Our study reiterates that PARKIN mutations represent a frequent cause of early-onset and familial parkinsonism. Some features like limb dystonia and psychiatric symptoms are typical, but notable new phenotypic features like excessive sweating, stereotypy and levodopa responsive retropulsion were observed in some patients, which contribute significantly to the phenotypic spectra of PARKIN mutations.

References: 1. Khan NL, Graham E, Critchley P, Schrag AE, Wood NW, Lees AJ, Bhatia KP, Quinn N. Parkin disease: a phenotypic study of a large case series. Brain. 2003 Jun;126(Pt 6):1279-92. 2. Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4.

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/expanding-the-canvas-of-parkin-mutations-and-clinical-phenotypes-in-familial-and-early-onset-parkinsons-disease-patients/