Long-read sequencing revealing intragenic deletions in exome-negative spastic paraplegias.
J Hum Genet
; 68(10): 689-697, 2023 Oct.
Article
in En
| MEDLINE
| ID: mdl-37308565
ABSTRACT
Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. To date, a total of 88 types of SPG are known. To diagnose HSP, multiple technologies, including microarray, direct sequencing, multiplex ligation-dependent probe amplification, and short-read next-generation sequencing, are often chosen based on the frequency of HSP subtypes. Exome sequencing (ES) is commonly used. We used ES to analyze ten cases of HSP from eight families. We identified pathogenic variants in three cases (from three different families); however, we were unable to determine the cause of the other seven cases using ES. We therefore applied long-read sequencing to the seven undetermined HSP cases (from five families). We detected intragenic deletions within the SPAST gene in four families, and a deletion within PSEN1 in the remaining family. The size of the deletion ranged from 4.7 to 12.5 kb and involved 1-7 exons. All deletions were entirely included in one long read. We retrospectively performed an ES-based copy number variation analysis focusing on pathogenic deletions, but were not able to accurately detect these deletions. This study demonstrated the efficiency of long-read sequencing in detecting intragenic pathogenic deletions in ES-negative HSP patients.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spastic Paraplegia, Hereditary
/
Adenosine Triphosphatases
Limits:
Humans
Language:
En
Journal:
J Hum Genet
Journal subject:
GENETICA MEDICA
Year:
2023
Document type:
Article
Affiliation country:
Japón