Role of chimeric transcript formation in the pathogenesis of birth defects.
Child, Preschool
Chromosome Banding
Craniofacial Abnormalities
/ diagnosis
Facies
Female
Gene Expression Profiling
Genetic Association Studies
/ methods
Genetic Diseases, Inborn
/ diagnosis
Genetic Predisposition to Disease
Genomics
/ methods
Hirschsprung Disease
/ diagnosis
Humans
Intellectual Disability
/ diagnosis
Microcephaly
/ diagnosis
Muscle Hypotonia
/ diagnosis
Mutant Chimeric Proteins
/ genetics
Transcription, Genetic
Transcriptome
Exome Sequencing
Whole Genome Sequencing
RNA-seq
chimeric transcript
fusion gene
whole genome sequence
Journal
Congenital anomalies
ISSN: 1741-4520
Titre abrégé: Congenit Anom (Kyoto)
Pays: Australia
ID NLM: 9306292
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
revised:
30
09
2020
received:
03
09
2020
accepted:
26
10
2020
pubmed:
30
10
2020
medline:
25
12
2021
entrez:
29
10
2020
Statut:
ppublish
Résumé
Chimeric transcripts are formed by chromosomal aberrations. Little is known about the role of chimeric transcripts in the pathogenesis of birth defects. We reanalyzed RNA-seq data in alignment map files from the peripheral blood of 56 patients in whom the diagnoses could not be confirmed by standard exome analysis and transcriptome analysis to screen for chimeric transcripts using a dedicated software, ChimPipe. Chimeric analysis led to a diagnosis in two of the 56 patients: (a) the first patient had a chimeric transcript spanning the causative gene ZEB2 and the GTDC1 gene in its neighboring locus. RNA-seq revealed reads spanning exon 5 of ZEB2 and exon 7 of GTDC1. Whole genome sequencing revealed a 436-kb deletion spanning intron 4 of ZEB2 and intron 7 of GTDC1 and the diagnosis of Mowat-Wilson syndrome was made. (b) The second patient had a chimeric transcript spanning the causative gene KCNK9 and the TRAPPC9 gene in its neighboring locus. RNA-seq revealed reads spanning exon 21 of TRAPPC9 and exon 1 of KCNK9. Whole genome sequencing revealed a 186-kb deletion spanning intron 20 of TRAPPC9 and intron 1 of KCNK9 in this patient. KCNK9 gene is a maternally expressed imprinted gene. The diagnosis of Birk-Barel syndrome was made. Thus, both patients had chimeric transcripts that were directly involved in the pathogenesis of the birth defects. The approach reported herein, of detecting chimeric transcripts from RNA-seq data, is unique in that the approach does not rely on any prior information on the presence of genomic deletion.
Substances chimiques
Mutant Chimeric Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
76-81Subventions
Organisme : Initiative on Rare and Undiagnosed Diseases from the Japan Agency for Medical Research and Development
ID : JP17ek0109151
Organisme : JSPS KAKENHI, Grant-in-Aid for Early-Career Scientists
ID : JP19K17342
Organisme : Practical Research Project for Rare / Intractable Diseases from the Japan Agency for Medical Research and Development
ID : JP20ek0109485
Informations de copyright
© 2020 Japanese Teratology Society.
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