目的 探讨1例3-甲基戊烯二酸尿症Ⅶ型患儿的临床特征及基因变异特点。 方法 以2019年8月9日就诊于甘肃省妇幼保健院的1例患儿作为研究对象。收集患儿家系的临床资料，包括尿气相色谱质谱检测结果，应用全外显子组测序技术对患儿及其父母进行分析。 结果 患儿为女性，主要表现为出生后间断皮肤青紫，惊厥，低镁血症，呼吸暂停，中性粒细胞减少。尿液3-甲基戊烯二酸水平升高至17.53 μmol/L。基因测序结果提示患儿携带CLPB基因存在c.1016delT(p.L339Rfs*5)和c.1087A>G(p.R363G)复合杂合变异，分别遗传自其母亲和父亲，二者既往均未见报道。根据美国医学遗传学和基因组学学会(ACMG)相关指南，分别判定为致病变异和疑似致病变异。 结论 患儿被确诊为3-甲基戊烯二酸尿症Ⅶ型。c.1016delT和c.1087A>G变异的发现丰富了CLPB基因的变异谱。 Objective To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type Ⅶ. Methods A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. Results The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c. 1016delT (p.L339Rfs*5) and c. 1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. Conclusion The child was diagnosed with 3-methylglutenedioic aciduria type Ⅶ. Discovery of the c. 1016delT and c. 1087A>G variants has enriched the mutational spectrum of theCLPB gene.
Abstract
Objective To explore the clinical features and genetic basis for a child with 3-methylglutaconic aciduria type Ⅶ. Methods A child who was diagnosed at the Gansu Provincial Maternity and Child Health Care Hospital on August 9, 2019 was selected as the study subject. Clinical data of the child, including urine gas chromatography and mass spectrometry, were collected. The child and her parents were subjected to whole exome sequencing. Results The child, a female neonate, had presented mainly with intermittent skin cyanosis, convulsions, hypomagnesemia, apnea, neutropenia after birth. Her urine 3-methylpentenedioic acid has increased to 17.53 μmol/L. DNA sequencing revealed that she has harbored compound heterozygous variants of the CLPB gene, namely c. 1016delT (p.L339Rfs*5) and c. 1087A>G (p.R363G), which were respectively inherited from her mother and father. Both variants were unreported previously. Based on the standards from the American College of Medical Genetics and Genomics (ACMG), the variants were respectively predicted to be pathogenic and likely pathogenic. Conclusion The child was diagnosed with 3-methylglutenedioic aciduria type Ⅶ. Discovery of the c. 1016delT and c. 1087A>G variants has enriched the mutational spectrum of theCLPB gene.
关键词
3-甲基戊烯二酸尿症Ⅶ型/CLPB基因/全外显子组测序
Key words
3-methylglutaconic aciduria type Ⅶ/CLPB gene/Whole exome sequencing
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