medRxiv : the preprint server for health sciences · 2024
Long-read sequencing unravels the complexity of structural variants in PRKN in two individuals with early-onset Parkinson's disease.
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Cogan Guillaume, Daida Kensuke, Billingsley Kimberley J, Tesson Christelle, Forlani Sylvie, Jornea Ludmila, Arnaud Lionel, Tissier Laurene, LeGuern Eric, Singleton Andrew B, Ferrien Mélanie, Gervais Bernard Hélène, Lesage Suzanne, Blauwendraat Cornelis, Brice Alexis
Аннотация
BACKGROUND: PRKN biallelic pathogenic variants are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, the variants responsible for suspected PRKN- PD individuals are not always identified with standard genetic testing.
OBJECTIVES: Identify the genetic cause in two siblings with a PRKN -PD phenotype using long-read sequencing (LRS).
METHODS: The genetic investigation involved standard testing using successively multiple ligation probe amplification (MLPA), Sanger sequencing, targeted sequencing, whole-exome sequencing and LRS.
RESULTS: MLPA and targeted sequencing identified one copy of exon four in PRKN but no other variants were identified. Subsequently, LRS unveiled a large deletion encompassing exon 3 to 4 on one allele and a duplication of exon 3 on the second allele; explaining the siblings' phenotype. MLPA could not identify the balanced rearrangement of exon 3.
CONCLUSIONS: This study highlights the potential utility of long-read sequencing in the context of unsolved typical PRKN- PD individuals.
OBJECTIVES: Identify the genetic cause in two siblings with a PRKN -PD phenotype using long-read sequencing (LRS).
METHODS: The genetic investigation involved standard testing using successively multiple ligation probe amplification (MLPA), Sanger sequencing, targeted sequencing, whole-exome sequencing and LRS.
RESULTS: MLPA and targeted sequencing identified one copy of exon four in PRKN but no other variants were identified. Subsequently, LRS unveiled a large deletion encompassing exon 3 to 4 on one allele and a duplication of exon 3 on the second allele; explaining the siblings' phenotype. MLPA could not identify the balanced rearrangement of exon 3.
CONCLUSIONS: This study highlights the potential utility of long-read sequencing in the context of unsolved typical PRKN- PD individuals.