Evidence map›Paper›PMID 40858643›Full record

ArticleNPJ genomic medicine2025

Genome sequencing provides high diagnostic yield and new etiological insights for intellectual disability and developmental delay.

Kohei Hamanaka, Atsushi Fujita, Satoko Miyatake, Kazuharu Misawa, Eriko Koshimizu, Yuri Uchiyama, Naomi Tsuchida, Rie Seyama, Masamune Sakamoto, Kazuhiro Iwama and 57 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ genomic medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Identification of biallelic loss-of-functionJournal of medical genetics · 2026
    Article
  2. Article
  3. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

67 authors.

Kohei Hamanaka *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Atsushi Fujita *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Satoko Miyatake *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Kazuharu Misawa *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Eriko Koshimizu *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Yuri Uchiyama *Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Naomi TsuchidaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Rie SeyamaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Masamune SakamotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Kazuhiro IwamaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Naoto NishimuraDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Yasuhiro UtsunoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Li FuDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Marina TakizawaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Qiaowei LiangDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Toshiyuki ItaiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Ken SaidaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Sachiko OhoriDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Shinichi KameyamaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Hiromi FukudaDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Yukina HayashiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Yuta InoueDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Tomohide GotoDepartment of Neurology, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan.
Kazushi IchikawaDepartment of Neurology, Kanagawa Children's Medical Center, Yokohama, Kanagawa, Japan.
Ichiro KukiDepartment of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
Masataka FukuokaDepartment of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
Kiyohiro KimDepartment of Pediatric Neurology, Osaka City General Hospital, Osaka, Japan.
Tadashi ShiohamaDepartment of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Konomi ShimodaDepartment of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Kosuke OtsukaDepartment of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Yuki UedaDepartment of Pediatrics, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
Kazutoshi ChoMaternity and Perinatal Care Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
Kotaro YugeDepartment of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Nobutada TachiDepartment of Pediatrics, Sapporo Medical University School of Medicine, Sapporo, Japan, Hokkaido.
Masaki YoshidaDepartment of Pediatrics, Yakumo General Hospital, Futami, Hokkaido, Japan.
Atsuro DaidaDivision of Neurology, Saitama Children's Medical Center, Saitama, Japan.
Kyoko HirasawaDepartment of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
Tomoe YanagishitaDepartment of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
Toshiyuki YamamotoInstitute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan.
Kentaro ShiraiDepartment of Pediatrics, Tsuchiura Kyodo General Hospital, Tsuchiura, Ibaraki, Japan.
Tammar Fixler MehrMetabolic Neurogenetic Service, Wolfson Medical Center, Holon, Israel.
Aviva Fattal-ValevskiPediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv, Israel.
Dorit LevThe Rina Mor institute of Medical Genetics, Wolfson Medical Center, Holon, Israel.
Haruna YokoyamaDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Emi IwabuchiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yoshihiko SaitoDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Masaki MiuraDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Kenji SugaiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Akihiko IshiyamaDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Masayuki SasakiDepartment of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
Yoshihiro WatanabeChildren's Medical Center, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
Jun-Ichi TakanashiDepartment of Pediatrics, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Chiba, Japan.
Chong Ae KimGenetics Unit, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil.
Kenji YokochiDepartment of Pediatrics, Toyohashi Municipal Hospital, Toyohashi, Aichi, Japan.
Jun TohyamaDepartment of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital, Niigata, Japan.
Tatsuo MoriDepartment of Pediatrics, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Yuishin IzumiDepartment of Neurology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Yuiko HasegawaDepartment of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, Osaka, Japan.
Nobuhiko OkamotoDepartment of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, Osaka, Japan.
Takahiro IkedaDepartment of Pediatrics, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Hitoshi OsakaDepartment of Pediatrics, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Yosuke KawaiGenome Medical Science Project, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan.
Yosuke OmaeGenome Medical Science Project, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan.
Katsushi TokunagaGenome Medical Science Project, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan.
Mitsuhiro KatoDepartment of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
Takeshi MizuguchiDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Naomichi MatsumotoDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. naomat@yokohama-cu.ac.jp.

Funding

The AnVIL Data Ecosystem DACReS SupplementU24HG010262 · NHGRI · BROAD INSTITUTE, INC. · PI Robert J Carroll, Jonathan Lawson · 2018 to 2026
$40.5M
Japan Agency for Medical Research and Development JP24ek0109674Japan Society for the Promotion of Science JP22K15646Japan Society for the Promotion of Science JP22K15901Japan Society for the Promotion of Science JP23K27520Japan Society for the Promotion of Science JP23K27568Japan Society for the Promotion of Science JP24K02230NHGRI NIH HHS U24 HG010262
6 · The paper itself

Abstract

Short-read genome sequencing (GS) is a powerful technique for investigating the genetic etiologies of rare diseases, capturing diverse genetic variations that are challenging to approach with exome sequencing (ES). We performed GS on 260 families with intellectual disability/developmental delay. GS detected potentially disease-related variants in 55 of the 260 families, with structural resolution by long-read sequencing or optical genome mapping, and functional assessment by RNA sequencing. Excluding 31 theoretically ES-resolvable cases, GS yielded likely pathogenic variants in 17 of 229 as well as variants of unknown significance in 7 of 229, totaling 10.5%. These variants implicated several new etiological mechanisms: a microduplication syndrome involving ATP6V0C; disturbed interactions of TBL1XR1 and NR2F1 with putative cis-regulatory elements by chromosomal rearrangements; and a CCG repeat expansion near the CHD3 transcription start site. This study highlights the critical role of GS in clinical diagnostics and its potential to advance understanding of genetic disorders.

Identifiers

PMID40858643
PMCPMC12381280

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.