Scientific Reports (Aug 2022)
Whole-exome analysis of 177 pediatric patients with undiagnosed diseases
- Kotaro Narita,
- Hideki Muramatsu,
- Satoshi Narumi,
- Yuji Nakamura,
- Yusuke Okuno,
- Kyogo Suzuki,
- Motoharu Hamada,
- Naoya Yamaguchi,
- Atsushi Suzuki,
- Yosuke Nishio,
- Anna Shiraki,
- Ayako Yamamori,
- Yusuke Tsumura,
- Fumi Sawamura,
- Masahiro Kawaguchi,
- Manabu Wakamatsu,
- Shinsuke Kataoka,
- Kohji Kato,
- Hideyuki Asada,
- Tetsuo Kubota,
- Yukako Muramatsu,
- Hiroyuki Kidokoro,
- Jun Natsume,
- Seiji Mizuno,
- Tomohiko Nakata,
- Hidehito Inagaki,
- Naoko Ishihara,
- Takahiro Yonekawa,
- Akihisa Okumura,
- Tomoo Ogi,
- Seiji Kojima,
- Tadashi Kaname,
- Tomonobu Hasegawa,
- Shinji Saitoh,
- Yoshiyuki Takahashi
Affiliations
- Kotaro Narita
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Hideki Muramatsu
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Satoshi Narumi
- Department of Molecular Endocrinology, National Research Institute for Child Health
- Yuji Nakamura
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
- Yusuke Okuno
- Medical Genomics Center, Nagoya University Hospital
- Kyogo Suzuki
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Motoharu Hamada
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Naoya Yamaguchi
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
- Atsushi Suzuki
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
- Yosuke Nishio
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Anna Shiraki
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Ayako Yamamori
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Yusuke Tsumura
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Fumi Sawamura
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Masahiro Kawaguchi
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Manabu Wakamatsu
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Shinsuke Kataoka
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Kohji Kato
- Department of Genetics, Research Institute of Environmental Medicine, Nagoya University
- Hideyuki Asada
- Department of Pediatrics, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
- Tetsuo Kubota
- Department of Pediatrics, Anjo Kosei Hospital
- Yukako Muramatsu
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Hiroyuki Kidokoro
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Jun Natsume
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Seiji Mizuno
- Department of Clinical Genetics, Aichi Developmental Disability Center Central Hospital
- Tomohiko Nakata
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Hidehito Inagaki
- Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University
- Naoko Ishihara
- Department of Pediatrics, Fujita Health University School of Medicine
- Takahiro Yonekawa
- Department of Pediatrics, Mie University Graduate School of Medicine
- Akihisa Okumura
- Department of Pediatrics, Aichi Medical University
- Tomoo Ogi
- Department of Genetics, Research Institute of Environmental Medicine, Nagoya University
- Seiji Kojima
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- Tadashi Kaname
- Department of Genome Medicine, National Center for Child Health and Development
- Tomonobu Hasegawa
- Department of Pediatrics, Keio University School of Medicine
- Shinji Saitoh
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
- Yoshiyuki Takahashi
- Department of Pediatrics, Nagoya University Graduate School of Medicine
- DOI
- https://doi.org/10.1038/s41598-022-14161-6
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 1 – 8
Abstract
Abstract Recently, whole-exome sequencing (WES) has been used for genetic diagnoses of patients who remain otherwise undiagnosed. WES was performed in 177 Japanese patients with undiagnosed conditions who were referred to the Tokai regional branch of the Initiative on Rare and Undiagnosed Diseases (IRUD) (TOKAI-IRUD). This study included only patients who had not previously received genome-wide testing. Review meetings with specialists in various medical fields were held to evaluate the genetic diagnosis in each case, which was based on the guidelines of the American College of Medical Genetics and Genomics. WES identified diagnostic single-nucleotide variants in 66 patients and copy number variants (CNVs) in 11 patients. Additionally, a patient was diagnosed with Angelman syndrome with a complex clinical phenotype upon detection of a paternally derived uniparental disomy (UPD) [upd(15)pat] wherein the patient carried a homozygous DUOX2 p.E520D variant in the UPD region. Functional analysis confirmed that this DUOX2 variant was a loss-of-function missense substitution and the primary cause of congenital hypothyroidism. A significantly higher proportion of genetic diagnoses was achieved compared to previous reports (44%, 78/177 vs. 24–35%, respectively), probably due to detailed discussions and the higher rate of CNV detection.
