title: Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series.
abstract: Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication.
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan ; Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan ; Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Fukai
authors.affiliation: Division of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi 594-1101, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Okamoto
authors.affiliation: Hiroshima Municipal Center for Child Health and Development, Hiroshima 732-0052, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hiraki
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan ; Department of Molecular Neuropsychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ohi
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Taniike
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Mohri
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Nakashima
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku 236-0004, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, D3, 2-2, Yamadaoka, Suita 565-0871, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeda
keywords: Autism spectrum disorder; Copy-number variants; Duplication; Intelligence; Nephronophthisis 1 gene