Whole genome sequencing of 45 Japanese patients with intellectual disability

Intellectual disability (ID) is characterized by significant limitations in both intellectual functioning and adaptive behaviors, originating before the age of 18 years. However, the genetic etiologies of ID are still incompletely elucidated due to the wide range of clinical and genetic heterogeneit...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	American journal of medical genetics. Part A Ročník 185; číslo 5; s. 1468 - 1480
Hlavní autoři:	Abe‐Hatano, Chihiro, Iida, Aritoshi, Kosugi, Shunichi, Momozawa, Yukihide, Terao, Chikashi, Ishikawa, Keiko, Okubo, Mariko, Hachiya, Yasuo, Nishida, Hiroya, Nakamura, Kazuyuki, Miyata, Rie, Murakami, Chie, Takahashi, Kan, Hoshino, Kyoko, Sakamoto, Haruko, Ohta, Sayaka, Kubota, Masaya, Takeshita, Eri, Ishiyama, Akihiko, Nakagawa, Eiji, Sasaki, Masayuki, Kato, Mitsuhiro, Matsumoto, Naomichi, Kamatani, Yoichiro, Kubo, Michiaki, Takahashi, Yoshiyuki, Natsume, Jun, Inoue, Ken, Goto, Yu‐Ichi
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Hoboken, USA John Wiley & Sons, Inc 01.05.2021 Wiley Subscription Services, Inc Wiley
Témata:	ADNP protein Adolescent Cognitive ability Dyrk Kinases Exons Genetic diversity Genetic Heterogeneity Genetic Predisposition to Disease Genome, Human - genetics Genomes Heterozygote Homeodomain Proteins - genetics Homozygote Humans Intellectual disabilities intellectual disability Intellectual Disability - epidemiology Intellectual Disability - genetics Intellectual Disability - pathology intellectual disability‐associated gene Intelligence Japan - epidemiology Life Sciences likely pathogenic variant Male Original pathogenic variant Phenotypes Protein Serine-Threonine Kinases - genetics Protein-Tyrosine Kinases - genetics PTEN protein Whole Genome Sequencing Japan whole genome sequencing likely pathogenic variant pathogenic variant intellectual disability-associated gene intellectual disability
ISSN:	1552-4825, 1552-4833, 1552-4833
On-line přístup:	Získat plný text
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Intellectual disability (ID) is characterized by significant limitations in both intellectual functioning and adaptive behaviors, originating before the age of 18 years. However, the genetic etiologies of ID are still incompletely elucidated due to the wide range of clinical and genetic heterogeneity. Whole genome sequencing (WGS) has been applied as a single‐step clinical diagnostic tool for ID because it detects genetic variations with a wide range of resolution from single nucleotide variants (SNVs) to structural variants (SVs). To explore the causative genes for ID, we employed WGS in 45 patients from 44 unrelated Japanese families and performed a stepwise screening approach focusing on the coding variants in the genes. Here, we report 12 pathogenic and likely pathogenic variants: seven heterozygous variants of ADNP, SATB2, ANKRD11, PTEN, TCF4, SPAST, and KCNA2, three hemizygous variants of SMS, SLC6A8, and IQSEC2, and one homozygous variant in AGTPBP1. Of these, four were considered novel. Furthermore, a novel 76 kb deletion containing exons 1 and 2 in DYRK1A was identified. We confirmed the clinical and genetic heterogeneity and high frequency of de novo causative variants (8/12, 66.7%). This is the first report of WGS analysis in Japanese patients with ID. Our results would provide insight into the correlation between novel variants and expanded phenotypes of the disease.
Bibliografie:	Funding information Intramural Research Grants for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry, Japan, Grant/Award Number: 27‐6 30‐7 to Y.G.; 30‐9 to A.I.; Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University, Grant/Award Number: 2020, 2A19 to A.I.; the Construction of Integrated Database of Clinical and Genomics Information and Sustainable System for Promoting Genomic Medicine in Japan from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 18kk0205012s0303 to Y.G.; the Platform Program for Promotion of Genome Medicine from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 17km0405104h0005 to Y.G.; the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 17kk0205012h0002 to Y.G. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC8247954 Funding information Intramural Research Grants for Neurological and Psychiatric Disorders from the National Center of Neurology and Psychiatry, Japan, Grant/Award Number: 27‐6 30‐7 to Y.G.; 30‐9 to A.I.; Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University, Grant/Award Number: 2020, 2A19 to A.I.; the Construction of Integrated Database of Clinical and Genomics Information and Sustainable System for Promoting Genomic Medicine in Japan from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 18kk0205012s0303 to Y.G.; the Platform Program for Promotion of Genome Medicine from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 17km0405104h0005 to Y.G.; the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development, AMED, Grant/Award Number: 17kk0205012h0002 to Y.G.
ISSN:	1552-4825 1552-4833 1552-4833
DOI:	10.1002/ajmg.a.62138