Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review.
Pathogenic variants of ornithine transcarbamylase deficiency: Nation-wide study in Japan and literature review.
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DOI：
10.3389/fgene.2022.952467
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发表时间：
2022
影响因子：
3.7
通讯作者：
Nakamura, Kimitoshi
中科院分区：
文献类型：
--
作者：
Kido, Jun;Sugawara, Keishin;Sawada, Takaaki;Matsumoto, Shirou;Nakamura, Kimitoshi
关键词：
鸟氨酸转氨甲酰酶缺乏症（OTCD）是一种X连锁疾病。一些患有OTCD的男性患者在新生儿期患有严重的高氨血症危象，而其他患者则出现迟发性表现，包括高氨血症昏迷。OTC基因中具有杂合致病性变体的女性可能会出现各种临床表现，从无症状的状况到严重的高氨血症发作，这是由于偏lyonization。我们报告了通过在日本进行的全国性调查在尿素循环障碍患者中检测到的CPS 1、ASS、ASL和OTC变异体。在本研究中，我们更新了日本患者的OTC变异数据，并通过广泛的文献综述从OTCD患者中获得了有关OTC遗传变异的信息。523个变异体包括386个取代（330个错义、53个无义和3个沉默）、8个缺失、2个重复、1个缺失-插入、55个移码、2个延伸和69个无类别（1个调节和68个剪接位点错误）突变。我们在男性OTCD患者中观察到发病时间（新生儿发病或晚发）、严重程度和基因突变之间的基因型-表型关系，因为OTC的失活水平显著依赖于致病性OTC变体。总之，关于OTC的遗传信息可能有助于预测OTCD患者的长期结局并确定具体的治疗策略，如肝移植。
Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder. Several male patients with OTCD suffer from severe hyperammonemic crisis in the neonatal period, whereas others develop late-onset manifestations, including hyperammonemic coma. Females with heterozygous pathogenic variants in the OTC gene may develop a variety of clinical manifestations, ranging from asymptomatic conditions to severe hyperammonemic attacks, owing to skewed lyonization. We reported the variants of CPS1, ASS, ASL and OTC detected in the patients with urea cycle disorders through a nation-wide survey in Japan. In this study, we updated the variant data of OTC in Japanese patients and acquired information regarding genetic variants of OTC from patients with OTCD through an extensive literature review. The 523 variants included 386 substitution (330 missense, 53 nonsense, and 3 silent), eight deletion, two duplication, one deletion-insertion, 55 frame shift, two extension, and 69 no category (1 regulatory and 68 splice site error) mutations. We observed a genotype–phenotype relation between the onset time (neonatal onset or late onset), the severity, and genetic mutation in male OTCD patients because the level of deactivation of OTC significantly depends on the pathogenic OTC variants. In conclusion, genetic information about OTC may help to predict long-term outcomes and determine specific treatment strategies, such as liver transplantation, in patients with OTCD.
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影响因子：
3.8
作者：
Bisanzi, S;Morrone, A;Zammarchi, E
通讯作者：
Zammarchi, E
影响因子：
3.8
作者：
Ensenauer, R;Tuchman, M;Babovic-Vuksanovic, D
通讯作者：
Babovic-Vuksanovic, D
影响因子：
3.1
作者：
Fantur, Michaela;Karall, Daniela;Fruehwirth, Martin
通讯作者：
Fruehwirth, Martin
影响因子：
3.7
作者：
Cavicchi C;Donati M;Parini R;Rigoldi M;Bernardi M;Orfei F;Gentiloni Silveri N;Colasante A;Funghini S;Catarzi S;Pasquini E;la Marca G;Mooney S;Guerrini R;Morrone A
通讯作者：
Morrone A
影响因子：
25.7
作者：
Ben-Ari, Ziv;Dalal, Adam;Mandel, Hanna
通讯作者：
Mandel, Hanna