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Molecular diagnosis of 405 individuals with autism spectrum disorder.
Miyake, Noriko; Tsurusaki, Yoshinori; Fukai, Ryoko; Kushima, Itaru; Okamoto, Nobuhiko; Ohashi, Kei; Nakamura, Kazuhiko; Hashimoto, Ryota; Hiraki, Yoko; Son, Shuraku; Kato, Mitsuhiro; Sakai, Yasunari; Osaka, Hitoshi; Deguchi, Kimiko; Matsuishi, Toyojiro; Takeshita, Saoko; Fattal-Valevski, Aviva; Ekhilevitch, Nina; Tohyama, Jun; Yap, Patrick; Keng, Wee Teik; Kobayashi, Hiroshi; Takubo, Keiyo; Okada, Takashi; Saitoh, Shinji; Yasuda, Yuka; Murai, Toshiya; Nakamura, Kazuyuki; Ohga, Shouichi; Matsumoto, Ayumi; Inoue, Ken; Saikusa, Tomoko; Hershkovitz, Tova; Kobayashi, Yu; Morikawa, Mako; Ito, Aiko; Hara, Toshiro; Uno, Yota; Seiwa, Chizuru; Ishizuka, Kanako; Shirahata, Emi; Fujita, Atsushi; Koshimizu, Eriko; Miyatake, Satoko; Takata, Atsushi; Mizuguchi, Takeshi; Ozaki, Norio; Matsumoto, Naomichi.
Afiliação
  • Miyake N; Department of Human Genetics, National Center for Global Health and Medicine, Tokyo, Japan. nomiyake@ri.ncgm.go.jp.
  • Tsurusaki Y; Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. nomiyake@ri.ncgm.go.jp.
  • Fukai R; Faculty of Nutritional Science, Sagami Women's University, Sagamihara, Japan.
  • Kushima I; Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
  • Okamoto N; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Ohashi K; Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan.
  • Nakamura K; Department of Medical Genetics, Osaka Women's and Children's Hospital, Osaka, Japan.
  • Hashimoto R; Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Hiraki Y; Department of Neuropsychiatry, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
  • Son S; Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
  • Kato M; Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
  • Sakai Y; Hiroshima Municipal Center for Child Health and Development, Hiroshima, Japan.
  • Osaka H; Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Deguchi K; Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan.
  • Matsuishi T; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Takeshita S; Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan.
  • Fattal-Valevski A; Deguchi Pediatric Clinic, Omura, Japan.
  • Ekhilevitch N; Departments of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
  • Tohyama J; Department of Pediatrics, St. Mary's Hospital, Kurume, Japan.
  • Yap P; Department of Pediatrics, Yokohama City University Medical Center, Yokohama, Japan.
  • Keng WT; Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Kobayashi H; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
  • Takubo K; Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital, Niigata, Japan.
  • Okada T; Genetic Health Service New Zealand, Auckland, New Zealand.
  • Saitoh S; Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
  • Yasuda Y; Genetic Department, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
  • Murai T; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Nakamura K; Department of Stem Cell Biology, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Ohga S; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Matsumoto A; Department of Developmental Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
  • Inoue K; Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
  • Saikusa T; Department of Pathology of Mental Diseases, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
  • Hershkovitz T; Department of Psychiatry, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • Kobayashi Y; Department of Pediatrics, Yamagata University Faculty of Medicine, Yamagata, Japan.
  • Morikawa M; Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • Ito A; Department of Pediatrics, Jichi Medical University, Shimotsuke, Japan.
  • Hara T; Deguchi Pediatric Clinic, Omura, Japan.
  • Uno Y; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan.
  • Seiwa C; Departments of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan.
  • Ishizuka K; Department of Pediatrics, St. Mary's Hospital, Kurume, Japan.
  • Shirahata E; The Genetics Institute, Rambam Health Care Campus, Haifa, Israel.
  • Fujita A; Department of Child Neurology, National Hospital Organization Nishiniigata Chuo Hospital, Niigata, Japan.
  • Koshimizu E; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Miyatake S; Department of Pediatrics, Yamagata Prefectural Rehabilitation Center for Children with Disabilities, Yamagata, Japan.
  • Takata A; Fukuoka Children's Hospital, Fukuoka, Japan.
  • Mizuguchi T; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
  • Ozaki N; Department of Pediatrics, Yamagata Prefectural Rehabilitation Center for Children with Disabilities, Yamagata, Japan.
  • Matsumoto N; Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Eur J Hum Genet ; 2023 Mar 27.
Article em En | MEDLINE | ID: mdl-36973392
Autism spectrum disorder (ASD) is caused by combined genetic and environmental factors. Genetic heritability in ASD is estimated as 60-90%, and genetic investigations have revealed many monogenic factors. We analyzed 405 patients with ASD using family-based exome sequencing to detect disease-causing single-nucleotide variants (SNVs), small insertions and deletions (indels), and copy number variations (CNVs) for molecular diagnoses. All candidate variants were validated by Sanger sequencing or quantitative polymerase chain reaction and were evaluated using the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines for molecular diagnosis. We identified 55 disease-causing SNVs/indels in 53 affected individuals and 13 disease-causing CNVs in 13 affected individuals, achieving a molecular diagnosis in 66 of 405 affected individuals (16.3%). Among the 55 disease-causing SNVs/indels, 51 occurred de novo, 2 were compound heterozygous (in one patient), and 2 were X-linked hemizygous variants inherited from unaffected mothers. The molecular diagnosis rate in females was significantly higher than that in males. We analyzed affected sibling cases of 24 quads and 2 quintets, but only one pair of siblings shared an identical pathogenic variant. Notably, there was a higher molecular diagnostic rate in simplex cases than in multiplex families. Our simulation indicated that the diagnostic yield is increasing by 0.63% (range 0-2.5%) per year. Based on our simple simulation, diagnostic yield is improving over time. Thus, periodical reevaluation of ES data should be strongly encouraged in undiagnosed ASD patients.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Guideline / Prognostic_studies Idioma: En Revista: Eur J Hum Genet Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Guideline / Prognostic_studies Idioma: En Revista: Eur J Hum Genet Ano de publicação: 2023 Tipo de documento: Article