The first report of Japanese patients with asparagine synthetase deficiency
The first report of Japanese patients with asparagine synthetase deficiency
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DOI：
10.1016/j.braindev.2016.09.010
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发表时间：
2017-03-01
影响因子：
1.7
通讯作者：
Fukao, Toshiyuki
中科院分区：
文献类型：
--
作者：
Yamamoto, Takahiro;Endo, Wakaba;Fukao, Toshiyuki
背景：天冬酰胺合成酶(ASNS)缺乏症是最近发现的一种非必需氨基酸代谢紊乱，表现为严重的进行性小头畸形、智能障碍、运动性四肢瘫痪和顽固性癫痫。方法：对2例日本儿童进展性小头畸形进行全外显子测序分析，发现新的ASNS突变。通过结构评估和计算机预测分析ASNS突变的影响。结果：我们描述了第一例已知的日本ASNS缺乏症患者。他们的临床表现与报道的ASNS缺乏症非常相似。1例患者在产前发现进行性小头畸形，而2例患者出生后才发现进行性小头畸形。两例患者都有新的ASNS突变：患者1携带母亲遗传的p.L145S和p.L247W，而患者2携带母亲和父亲分别遗传的p.V489D和p.W541Cfs*5。四个突变中的三个被预测会影响蛋白质折叠，在计算机分析中，它们可能是致病的。结论：我们报告了头两例日本ASNS缺乏症患者。疾病的严重程度似乎因患者而异，其他非必需氨基酸代谢紊乱的情况也是如此。(C)2016年日本儿童神经病学学会。爱思唯尔出版，版权所有。
Background: 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.Methods: 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.Results: 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.Conclusion: 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. (C) 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.