Long-read sequencing unravels the complexity of structural variants in PRKN in two individuals with early-onset Parkinson's disease.
medRxiv
; 2024 May 03.
Article
en En
| MEDLINE
| ID: mdl-38746197
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
MedRxiv
Año:
2024
Tipo del documento:
Article