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目的报告GFM1突变所致疾病的临床特征及验证基因型和临床表型关系。方法回顾性分析1例门诊就诊的GFM1基因突变儿童的临床及基因突变资料,结合文献归纳GFM1基因突变的临床特点,构建编码线粒体翻译因子G1(mt EFG1)空间结构图,检验GFM1基因错义突变位置与临床表型关系的假说。结果患儿,女,6个月28 d。生长发育迟缓,急性肝衰竭。体格检查:反应差,嗜睡,全身皮肤黏膜黄染,腹平软,肝脾肿大。辅助检查:总胆红素、直接胆红素、转氨酶、碱性磷酸酶、血清γ-谷氨酰转肽酶和血氨升高,白蛋白下降,凝血酶原时间延长,血糖下降,酸中毒,血乳酸升高,血浆氨基酸及酰基肉碱谱示血中多种氨基酸升高,尿有机酸检查提示酮尿,头颅MRI示双侧丘脑、大脑脚、基底节区、枕叶前内侧异常信号。GFM1基因的复合杂合突变,第5外显子c.688G>A点突变致蛋白质改变为p.Gly230Ser;第14外显子c.1686del G的移码突变致蛋白质改变为p.Asp563Thrfs*24。mt EFG1空间结构图显示,p.Gly230Ser处于蛋白周边位置,预测表现应该为脑型。结论 1例携带GFM1基因复合杂合突变(c.688G>A和c.1686del G)的中国儿童,其临床表现为急性肝衰竭,不支持以往GFM1基因错义突变导致蛋白周边位置的氨基酸改变时临床表现为脑型的假设。
Objective To report the clinical characteristics of GFM1 mutation-related diseases and to verify the relationship between genotypes and clinical phenotypes. Methods A retrospective analysis of clinical and gene mutation data of 1 outpatient clinic with GFM1 gene mutation was performed. The spatial structure of mitochondrial translocation factor G1 (mt EFG1) was constructed according to the clinical characteristics of GFM1 gene mutation. The missense mutation of GFM1 gene Hypotheses about the relationship between location and clinical phenotype. Results children, women, 6 months 28 d. Growth retardation, acute liver failure. Physical examination: poor response, lethargy, systemic skin mucosa yellow dye, abdominal soft, hepatosplenomegaly. Auxiliary examination: total bilirubin, direct bilirubin, transaminase, alkaline phosphatase, serum γ-glutamyl transpeptidase and elevated serum ammonia, albumin decreased prothrombin time, decreased blood glucose, acidosis , Elevated blood lactate, plasma amino acids and acylcarnitine spectrum showed a variety of amino acids in the blood, urinalysis showed urine ketones, head MRI showed bilateral thalamus, cerebral peduncle, basal ganglia, medial anterior occipital lobe signal . GFM1 gene heterozygous mutation, exon 5 c.688G> A point mutations caused by the protein to p.Gly230Ser; exon 14 c.1686del G frameshift mutation-causing protein changes to p.Asp563Thrfs * 24 . The mt EFG1 spatial structure map shows that p.Gly230Ser is located at the periphery of the protein and the prediction should be brain type. CONCLUSIONS: A Chinese child carrying a composite heterozygous mutation of GFM1 gene (c.688G> A and c.1686del G) has clinical manifestations of acute liver failure and does not support past amino acid changes in the periphery of the protein due to missense mutations in the GFM1 gene Clinical manifestations of brain hypothesis.