Homozygous splicing mutation in NUP133 causes Galloway–Mowat syndrome
Correction(s) for this article
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Correction
- Volume 85Issue 3Annals of Neurology
- pages: 462-463
- First Published online: February 28, 2019
Atsushi Fujita PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorCorresponding Author
Hiroyasu Tsukaguchi MD, PhD
Second Department of Internal Medicine, Kansai Medical University, Osaka
Address correspondence to Dr Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; E-mail: [email protected] and Dr Tsukaguchi, Second Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka, 573-1191 Japan; E-mail: [email protected]Search for more papers by this authorEriko Koshimizu PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorHitoshi Nakazato MD, PhD
Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorKyoko Itoh MD, PhD
Department of Pathology and Applied Neurobiology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto
Search for more papers by this authorShohei Kuraoka MD
Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorYoshihiro Komohara MD, PhD
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorMasaaki Shiina MD, PhD
Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorShohei Nakamura BS
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorMika Kitajima MD, PhD
Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorYoshinori Tsurusaki PhD
Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama
Search for more papers by this authorSatoko Miyatake MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorKazuhiro Ogata MD, PhD
Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorKazumoto Iijima MD, PhD
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorCorresponding Author
Naomichi Matsumoto MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Address correspondence to Dr Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; E-mail: [email protected] and Dr Tsukaguchi, Second Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka, 573-1191 Japan; E-mail: [email protected]Search for more papers by this authorNoriko Miyake MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorAtsushi Fujita PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorCorresponding Author
Hiroyasu Tsukaguchi MD, PhD
Second Department of Internal Medicine, Kansai Medical University, Osaka
Address correspondence to Dr Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; E-mail: [email protected] and Dr Tsukaguchi, Second Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka, 573-1191 Japan; E-mail: [email protected]Search for more papers by this authorEriko Koshimizu PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorHitoshi Nakazato MD, PhD
Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorKyoko Itoh MD, PhD
Department of Pathology and Applied Neurobiology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto
Search for more papers by this authorShohei Kuraoka MD
Department of Pediatrics, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorYoshihiro Komohara MD, PhD
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorMasaaki Shiina MD, PhD
Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorShohei Nakamura BS
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorMika Kitajima MD, PhD
Department of Diagnostic Radiology, Faculty of Life Sciences, Kumamoto University, Kumamoto
Search for more papers by this authorYoshinori Tsurusaki PhD
Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama
Search for more papers by this authorSatoko Miyatake MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorKazuhiro Ogata MD, PhD
Department of Biochemistry, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorKazumoto Iijima MD, PhD
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
Search for more papers by this authorCorresponding Author
Naomichi Matsumoto MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Address correspondence to Dr Matsumoto, Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan; E-mail: [email protected] and Dr Tsukaguchi, Second Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-machi, Hirakata-shi, Osaka, 573-1191 Japan; E-mail: [email protected]Search for more papers by this authorNoriko Miyake MD, PhD
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama
Search for more papers by this authorA.F., H.T., and E.K. contributed equally.
Abstract
Objective
Galloway–Mowat syndrome (GAMOS) is a neural and renal disorder, characterized by microcephaly, brain anomalies, and early onset nephrotic syndrome. Biallelic mutations in WDR73 and the 4 subunit genes of the KEOPS complex are reported to cause GAMOS. Furthermore, an identical homozygous NUP107 (nucleoporin 107kDa) mutation was identified in 4 GAMOS-like families, although biallelic NUP107 mutations were originally identified in steroid-resistant nephrotic syndrome. NUP107 and NUP133 (nucleoporin 133kDa) are interacting subunits of the nuclear pore complex in the nuclear envelope during interphase, and these proteins are also involved in centrosome positioning and spindle assembly during mitosis.
Methods
Linkage analysis and whole exome sequencing were performed in a previously reported GAMOS family with brain atrophy and steroid-resistant nephrotic syndrome.
Results
We identified a homozygous NUP133 mutation, c.3335-11T>A, which results in the insertion of 9bp of intronic sequence between exons 25 and 26 in the mutant transcript. NUP133 and NUP107 interaction was impaired by the NUP133 mutation based on an immunoprecipitation assay. Importantly, focal cortical dysplasia type IIa was recognized in the brain of an autopsied patient and focal segmental glomerulosclerosis was confirmed in the kidneys of the 3 examined patients. A nup133-knockdown zebrafish model exhibited microcephaly, fewer neuronal cells, underdeveloped glomeruli, and fusion of the foot processes of the podocytes, which mimicked human GAMOS features. nup133 morphants could be rescued by human wild-type NUP133 mRNA but not by mutant mRNA.
Interpretation
These data indicate that the biallelic NUP133 loss-of-function mutation causes GAMOS. Ann Neurol 2018;84:814–828
Potential Conflicts of Interest
Nothing to report.
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