一例瓜氨酸血症Ⅰ型患儿的临床特点及ASS1基因突变分析  

Clinical and ASS1 mutation in a patient with Citrullinemia type Ⅰ

作　　者：孙媛媛[1] 陈翠娥 朱艳可[1] 朱融和[1] 周爱华[1] 王丹[1] SUN Yuan-yuan;CHEN Cui-e;ZHU Yan-ke;ZHU Rong-he;ZHOU Ai-hua;WANG Dan(Department of Pediatrics, The First Affiliated Hospital of Wenzhou MedicalUniversity,Wenzhou,China, 325000;Department of PediatricsYiwu Maternity and Children Hospital, Jinhua, China,322000)

机构地区：[1]温州医科大学附属第一医院儿科,浙江温州325015 [2]义乌市妇幼保健院新生儿科,浙江金华322000

出　　处：《中国优生与遗传杂志》2019年第6期668-670,678,共4页Chinese Journal of Birth Health & Heredity

基　　金：温州市科技局项目(Y20140497)

摘　　要：目的对一例临床怀疑瓜氨酸血症Ⅰ型患儿进行分子遗传学研究,明确致病突变,并对其相关的临床特点、转归进行总结。方法收集患儿的临床资料,提取患儿外周血DNA,应用高通量捕获测序确定患儿ASS1基因突变情况,并用Sanger测序验证测序结果以及ASS1基因的家系分析。结果患儿生后第6天出现体温不升、呻吟、喂养困难、惊厥,血氨明显升高(1240μmol/L),血串联质谱(MS/MS)分析提示血瓜氨酸显著升高(1979.03μmol/L),尿气相色谱/质谱(GC/MS)提示乳清酸升高,予限制蛋白饮食、精氨酸治疗后血氨恢复正常,神经系统损害持续加重,头颅MRI提示脑萎缩、脑软化明显,随访至12月时死亡。基因序列分析发现患儿ASS1基因存在c.910C>T和c.1087C>T复合杂合突变,其中c.910C>T突变来源于父亲、c.1087C>T突变来源于母亲。c.910C>T突变导致第304号氨基酸由精氨酸变异为色氨酸,c.1087C>T突变导致第363号氨基酸由精氨酸变异为色氨酸,为错义突变。结论通过高通量捕获测序和Sanger测序确定了一例瓜氨酸血症Ⅰ型患儿的致病基因,随访发现该复合杂合突变引起的瓜氨酸血症患儿临床表现重,预后极差。Objective:To study molecular genetics of a clinically suspected citrullinemia type I,to identify pathogenic mutations,and to summary clinical features and outcomes. Methods:Clinical data of the patient were collected,peripheral blood DNA was extracted,high-throughput capture sequencing was used to determine the mutation status of ASS1 gene in the patient,the sequencing results and the family analysis of ASS1 gene were verified by Sanger sequencing. Results:Hypothermia,moaning,feeding difficulties and convulsion occurred on the 6 th day after birth,blood ammonia was significantly increased(1240 μmol/L),blood tandem mass spectrometry(MS/MS)indicated that citrulline was significantly increased(1 979.03 μmol/L),and urine gas chromatography/mass spectrometry(GC/MS)indicated that orotic acid was increased. The patient received the protein restriction diet and arginine treatment,the blood ammonia returned to normal,and the neurological damage continued to worsen. Cranial MRI showed obvious brain atrophy and brain softening,and the patient died in the follow-up to 12 month. The analysis of high-throughput capture sequencing showed that c.910 C>T and c.1087 C>T heterozygous mutation in ASS1 gene,in which c.910 C>T mutation originated from the father and c.1087 C>T mutation originated from the mother. The c.910 C>T mutation leads to the mutation of no. 304 amino acid from arginine to tryptophan,and c.1087 C>T mutation leads to the mutation of no. 363 amino acid from arginine to tryptophan,all are missense mutation. Conclusion:A pathogenic gene of a patient with citrullinemia I was determined by high-throughput capture sequencing and Sanger sequencing. The patient with citrullinemia caused by this complex heterozygosis gene mutation presented severe clinical manifestations and poor prognosis.

关 键 词：瓜氨酸血症Ⅰ型 ASS1基因 高通量捕获测序 Sanger测序 

分 类 号：R394.3[医药卫生—医学遗传学]