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中国循证儿科杂志

中国循证儿科杂志 ›› 2017, Vol. 12 ›› Issue (1): 49-53.

• 论著 • 上一篇    下一篇

COG6基因新突变致新生儿期起病的先天性糖基化障碍1例并文献复习

吴冰冰1,李宛星1,杨琳,王慧君,周文浩   

  1. 复旦大学附属儿科医院分子诊断中心，上海市出生缺陷防治重点实验室 上海，201102；1  共同第一作者
  • 收稿日期:2017-01-17 修回日期:2017-03-13 出版日期:2017-02-25 发布日期:2017-02-25
  • 通讯作者: 杨琳

A case of neonatal congenital disorders of glycosylation caused by COG6 gene mutation and literature review

WU Bing-bing1, LI Wan-xing1, YANG Lin, WANG Hui-jun, ZHOU Wen-hao   

  1. The Molecular Genetic Diagnosis Center, Shanghai Key Lab of Birth Defect, Children's Hospital of Fudan University, Shanghai 201102, China; 1 Co-first author
  • Received:2017-01-17 Revised:2017-03-13 Online:2017-02-25 Published:2017-02-25
  • Contact: YANG Lin

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摘要：

目的：诊断1例COG6基因复合杂合突变所致的先天性糖基化障碍（CDG），为CDG患儿的的早期诊断、制定干预措施和结局预测提供依据。方法： 总结1例携带有COG6复合杂合突变的CDG患儿的临床表型、家系sanger验证信息、影像学表现、实验室检查和随访信息，对COG6及其他Golgi复合体（COG）基因突变所致CDG的疾病表型行文献复习。结果：患儿因早产、生后反复气促吐沫1月余就诊，主要表现为不明原因反复高热伴肝酶异常，皮肤少汗，异常面容，并存在心、肺、肾、凝血和神经系统异常。行核心家系全外显子组检测发现COG6基因复合杂合突变c.511C>T （p.R171X）和c.540G>A （p.E180E），c.511C>T 来源于母亲，是人类基因突变数据库（HGMD）已报道的CDGⅡ型的致病突变；c.540G>A 来源于父亲，为新发突变。汇总专业版HGMD已报道的COG6-CDG 患儿9例加本文1例共10例表型（CDGⅡ型），异常面容，可表现为肝、皮肤、心脏、肾脏、骨骼、关节、凝血、免疫、神经系、听力和视觉异常或其他畸形等，多数患儿生长发育迟缓，预后不良，5例病死，存活者均进展为严重肝功能障碍伴反复感染。比COG-CDG其他亚型，临床表现更丰富、病情偏重且预后差。结论：新生儿期表现为不明原因高热伴肝酶异常，皮肤少汗，肌张力异常，或存在心、肾、免疫和凝血等多器官和系统功能异常的患儿，应高度怀疑COG6-CDG，此类患儿多数生长发育迟缓，预后不良，新生儿期通过基因测序可早期诊断。

Abstract:

Objective: To diagnose a neonate as congenital disorders of glycosylation caused by COG6 gene mutation (COG6-CDG), summarize and compare clinical features of 7 subtypes of CDGs caused by mutations of Golgi complex (COG), and to provide the basis for accurate diagnosis, clinical decision-making and outcome prediction of COG-CDGs. Methods: Analysis was performed on clinical features, parental sanger test, imageological examination, laboratory test and follow-up of a patient carrying a pair of compound heterozygous mutations of COG6, and literatures about clinical features of CDGs caused by COG6 and other COGs were reviewed. Results: The patient presented with recurrent hyperpyrexia, elevated liver enzymes, congenital heart disease, prolonged APTT, multiple small lesions in left kidney, micrognathia, no calcification of second molar, eosinophil deficiency. A pair of compound heterozygous mutations of COG6 was found by WES. c.511C>T p.R171X was from mother and was reported as a pathogenic mutation of COG6-CDG by HGMD, while c.540G>A p.E180E was from father and was a novel splicing mutation. Nine patients were reported as COG6-CDG listed by HGMD, clinical features were liver dysfunction, abnormal growth and development, facial abnormalities, recurrent hyperpyrexia, hypohidrosis, skin abnormalities, congenital heart disease, renal abnormalities, coagulation abnormalities, abnormal immune system, skeletal joint deformities, seizures, abnormal brain MRI, hearing or visual abnormalities or other malformations, more than half patients died and the rest survivors progressed to severe liver dysfunction with recurrent infections. Conclusion: The first case of COG6-CDG is diagnosed and reported in China, COG6-CDG is a rare genetic disease involving multiple organ systems, hypohidrotic ectodermal dysplasia with liver enzyme abnormalities is its main clinical features, most patients present with abnormal growth and development, and poor prognosis. Neonatal gene sequencing can help diagnose COG-CDG and provide the basis for accurate diagnosis, clinical decision-making and outcome prediction of COG-CDGs.

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