Objective: We report the clinical and genetic findings of two siblings who presented with early-onset Parkinson’s disease (PD) and had two distinct parkin mutations, a duplication and a deletion.

Background: Familial forms constitute 10% of all PD cases with a wide spectrum of genetic causes. In Turkey, PARK2 is the most frequently encountered autosomal recessive PD subtype.

Methods: The immediate family consists of non-consanguineous parents originating from the same geographical region of Turkey and three offsprings. Two affected siblings (a male and a female) were examined and followed for young onset PD in our clinic. Family history revealed PD in paternal aunt beginning at the age of 50 years, who was reported to have died due to complications of PD. Because of family history and young disease onset (35 and 40 years), we referred the patients to genetic analysis. The index case’s and his older sister’s DNA samples were subjected to parkin gene sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis.

Results: MLPA analysis revealed a PARK2/Exon7-8-9 duplication and a PARK2/Exon7 deletion in compound heterozygous form in both patients. The father was heterozygous for the duplication, the mother and the unaffected sibling were heterozygous for the deletion.

Conclusions: We want to emphasize the compound heterozygous presence of two rare parkin mutations in two siblings from Turkey, resulting in an early onset PD with a typical autosomal recessive type of inheritance. Parents and the unaffected sibling are only carriers and are thus not expected to develop PD. Unfortunately, we cannot tell anything about the genotype of the paternal aunt, who succumbed to PD, since we do not have her sample.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/young-onset-parkinsons-disease-in-two-siblings-with-compound-heterozygosity-for-two-rare-parkin-mutations/