Title |
The first report of Japanese patients with asparagine synthetase deficiency
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Published in |
Brain & Development, October 2016
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DOI | 10.1016/j.braindev.2016.09.010 |
Pubmed ID | |
Authors |
Takahiro Yamamoto, Wakaba Endo, Hidenori Ohnishi, Kazuo Kubota, Norio Kawamoto, Takehiko Inui, Atsushi Imamura, Jun-ichi Takanashi, Masaaki Shiina, Hirotomo Saitsu, Kazuhiro Ogata, Naomichi Matsumoto, Kazuhiro Haginoya, Toshiyuki Fukao |
Abstract |
Asparagine synthetase (ASNS) deficiency was recently discovered as a metabolic disorder of non-essential amino acids, and presents as severe progressive microcephaly, intellectual disorder, dyskinetic quadriplegia, and intractable seizures. Two Japanese children with progressive microcephaly born to unrelated patients were analyzed by whole exome sequencing and novel ASNS mutations were identified. The effects of the ASNS mutations were analyzed by structural evaluation and in silico predictions. We describe the first known Japanese patients with ASNS deficiency. Their clinical manifestations were very similar to reported cases of ASNS deficiency. Progressive microcephaly was noted during the prenatal period in patient 1 but only after birth in patient 2. Both patients had novel ASNS mutations: patient 1 had p.L145S transmitted from his mother and p.L247W which was absent from his mother, while patient 2 carried p.V489D and p.W541Cfs*5, which were transmitted from his mother and father, respectively. Three of the four mutations were predicted to affect protein folding, and in silico analyses suggested that they would be pathogenic. We report the first two Japanese patients with ASNS deficiency. Disease severity appears to vary among patients, as is the case for other non-essential amino acid metabolic disorders. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Switzerland | 2 | 50% |
Turkey | 1 | 25% |
Unknown | 1 | 25% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 75% |
Scientists | 1 | 25% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 43 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 11 | 26% |
Student > Ph. D. Student | 4 | 9% |
Researcher | 3 | 7% |
Lecturer | 3 | 7% |
Student > Bachelor | 2 | 5% |
Other | 11 | 26% |
Unknown | 9 | 21% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 10 | 23% |
Psychology | 6 | 14% |
Biochemistry, Genetics and Molecular Biology | 4 | 9% |
Neuroscience | 4 | 9% |
Immunology and Microbiology | 1 | 2% |
Other | 5 | 12% |
Unknown | 13 | 30% |