一例肉碱棕榈酰转移酶1A缺乏症患儿的临床特点及基因突变分析

Clinical features and genetic analysis of a case with carnitine palmitoyltransferase 1A deficiency

目的分析1例肉碱棕榈酰转移酶1A（carnitine palmitoyltransferase 1A，CPTIA）缺乏症患儿的临床和基因突变特征，探讨其分子遗传学发病机制。方法收集患儿的临床资料，串联质谱分析血液酰基肉碱，提取患儿及父母外周血基因组DNA，应用PCR-直接测序法对CPT1A基因所有外显子及侧翼进行突变分析。结果测序结果显示患儿携带CPTIA基因c．1787T〉C（p．L596P）与c．2201T〉C（p．F734S）复合杂合突变，父亲携带c．1787T〉C（p．L596P）突变，母亲携带c．2201T〉C（p．F734S）突变。经检索dbSNP数据库、HGMD数据库及千人基因组数据库两个突变均为未报道过的新突变。生物学信息分析软件预测蛋白功能，提示均为致病突变。结论酰基肉碱分析是CPT1A缺乏症的主要诊断方法。CPT1A基因c．1787T〉C和c．2201T〉C突变可能为该患儿致病原因。上述发现丰富了CPT1A基因突变谱，并为家系遗传咨询及产前诊断提供依据。

Objective To analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A （CPT1A） deficiency. Methods Clinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPTIA gene were analyzed by PCR and Sanger sequencing. Results Analysis showed that the patient carried compound heterozygous mutations c. 1787T〉C and c. 2201T〉C of the CPTIA gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function, Conclusion Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c. 1787T〉C and c. 2201T〉C mutations of the CPTIA gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.