Novel ITPA variants identified by whole genome sequencing and RNA sequencing
© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics..
Approximately 80% of rare diseases have a genetic cause, and an accurate genetic diagnosis is necessary for disease management, prognosis prediction, and genetic counseling. Whole-exome sequencing (WES) is a cost-effective approach for exploring the genetic cause, but several cases often remain undiagnosed. We combined whole genome sequencing (WGS) and RNA sequencing (RNA-seq) to identify the pathogenic variants in an unsolved case using WES. RNA-seq revealed aberrant exon 4 and exon 6 splicing of ITPA. WGS showed a previously unreported splicing donor variant, c.263+1G>A, and a novel heterozygous deletion, including exon 6. Detailed examination of the breakpoint indicated the deletion caused by recombination between Alu elements in different introns. The proband was found to have developmental and epileptic encephalopathies caused by variants in the ITPA gene. The combination of WGS and RNA-seq may be effective in diagnosing conditions in proband who could not be diagnosed using WES.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Journal of human genetics - 68(2023), 9 vom: 18. Sept., Seite 649-652 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Omichi, Nanako [VerfasserIn] |
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| Links: |
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| Themen: |
EC 3.6.1.- |
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| Anmerkungen: |
Date Completed 28.08.2023 Date Revised 28.08.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s10038-023-01156-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357483669 |
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| 245 | 1 | 0 | |a Novel ITPA variants identified by whole genome sequencing and RNA sequencing |
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| 520 | |a © 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics. | ||
| 520 | |a Approximately 80% of rare diseases have a genetic cause, and an accurate genetic diagnosis is necessary for disease management, prognosis prediction, and genetic counseling. Whole-exome sequencing (WES) is a cost-effective approach for exploring the genetic cause, but several cases often remain undiagnosed. We combined whole genome sequencing (WGS) and RNA sequencing (RNA-seq) to identify the pathogenic variants in an unsolved case using WES. RNA-seq revealed aberrant exon 4 and exon 6 splicing of ITPA. WGS showed a previously unreported splicing donor variant, c.263+1G>A, and a novel heterozygous deletion, including exon 6. Detailed examination of the breakpoint indicated the deletion caused by recombination between Alu elements in different introns. The proband was found to have developmental and epileptic encephalopathies caused by variants in the ITPA gene. The combination of WGS and RNA-seq may be effective in diagnosing conditions in proband who could not be diagnosed using WES | ||
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| 700 | 1 | |a Nakama, Mina |e verfasserin |4 aut | |
| 700 | 1 | |a Sasai, Hideo |e verfasserin |4 aut | |
| 700 | 1 | |a Terazawa, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Kobayashi, Emiko |e verfasserin |4 aut | |
| 700 | 1 | |a Fushimi, Takuya |e verfasserin |4 aut | |
| 700 | 1 | |a Sugiyama, Yohei |e verfasserin |4 aut | |
| 700 | 1 | |a Ichimoto, Keiko |e verfasserin |4 aut | |
| 700 | 1 | |a Nitta, Kazuhiro R |e verfasserin |4 aut | |
| 700 | 1 | |a Yatsuka, Yukiko |e verfasserin |4 aut | |
| 700 | 1 | |a Ohtake, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Murayama, Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Okazaki, Yasushi |e verfasserin |4 aut | |
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