Phase Determination and Demonstration of Parental Mosaicism of Intragenic <i>PRKN</i> Deletions Initially Identified by Chromosomal Microarray Analysis.

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BackgroundAutosomal recessive juvenile Parkinson disease (ARJP) is an early-onset neurodegenerative disorder characterized by Parkinsonian motor symptoms with slow progression and preserved cognition. Biallelic pathogenic variants within the PRKN gene are associated with ARJP. Among PRKN pathogenic variants, deletions are a frequent occurrence and may be identified through chromosomal microarray testing.MethodsHere we present a case with two intragenic PRKN deletions initially identified as a secondary finding using chromosomal microarray. One deletion was paternally inherited and the second initially appeared to be de novo. In addition to microarray which initially identified the two deletions, long-range GAP-PCR and Sanger sequencing were used to further characterize the de novo deletion and phase of the deletions.ResultsMolecular characterization of the apparently de novo deletion demonstrated low-level maternal mosaicism of this deletion, thus proving that these deletions are in trans in the proband, yielding a diagnosis of autosomal recessive juvenile Parkinson disease.ConclusionsThis case highlights the utility of a diagnostic approach combining microarray, long-range PCR, and Sanger sequencing to establish the phase and confirm biallelic PRKN deletions in a patient with ARJP. Furthermore, these findings highlight the importance of investigating the possibility of parental mosaicism to determine the phase of autosomal recessive variants and establish accurate recurrence risks.

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