Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series

Yuka Yasuda, Ryota Hashimoto, Ryoko Fukai, Nobuhiko Okamoto, Yoko Hiraki, Hidenaga Yamamori, Michiko Fujimoto, Kazutaka Ohi, Masako Taniike, Ikuko Mohri, Mitsuko Nakashima, Yoshinori Tsurusaki, Hirotomo Saitsu, Naomichi Matsumoto, Noriko Miyake, Masatoshi Takeda

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.