Abstract：
OBJECTIVE: To analyze the clinical phenotype and genotypes of two children with Carnitine-acylcarnitine translocase deficiency (CACTD).
METHODS: Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.
RESULTS: Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c.49G>C (p.Gly17Arg) and c.106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c.199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c.106-2A>G and c.49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.49G>C (p.Gly17Arg), c.106-2A>G, and c.199-10T>G variants were classified as likely pathogenic (PM2_supporting+PP3+PM3_strong+PP4), pathogenic (PVS1+PM2_supporting+PM5+PP3), and pathogenic (PVS1+PM2_supporting+PP3+PP5), respectively.
CONCLUSIONS: Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.
METHODS: Two children diagnosed with CACTD at the Gansu Provincial Maternal and Child Health Care Hospital respectively on January 3 and November 19, 2018 were selected as the study subjects. Trio-whole exome sequencing (trio-WES) was carried out, and candidate variants were validated through Sanger sequencing and pathogenicity analysis.
RESULTS: Both children were males and had manifested mainly with hypoglycemia. Trio-WES and Sanger sequencing showed that child 1 had harbored compound heterozygous variants of the SLC25A20 gene, namely c.49G>C (p.Gly17Arg) and c.106-2A>G, which were inherited from his father and mother, respectively. Child 2 had harbored homozygous c.199-10T>G variants of the SLC25A20 gene, which were inherited from both of his parents. Among these, the c.106-2A>G and c.49G>C variants were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.49G>C (p.Gly17Arg), c.106-2A>G, and c.199-10T>G variants were classified as likely pathogenic (PM2_supporting+PP3+PM3_strong+PP4), pathogenic (PVS1+PM2_supporting+PM5+PP3), and pathogenic (PVS1+PM2_supporting+PP3+PP5), respectively.
CONCLUSIONS: Combined with their clinical phenotype and genetic analysis, both children were diagnosed with CACTD. Above finding has provided a basis for their treatment as well as genetic counseling and prenatal diagnosis for their families.
摘要：
目的：分析2例卡尼汀-酰基卡尼汀转位酶缺乏症(CACTD)患儿的临床表型和基因型。
方法：选取分别于2018年1月3日和11月19日在甘肃省妇幼保健院确诊为CACTD的2例患儿作为研究对象。进行三全外显子组测序(trio-WES),和候选变异体通过Sanger测序和致病性分析进行验证。
结果：两名儿童均为男性，主要表现为低血糖。Trio-WES和Sanger测序显示，儿童1具有SLC25A20基因的复合杂合变体，即c.49G>C（p。Gly17Arg）和c.106-2A>G，从他的父亲和母亲那里继承下来，分别。儿童2具有SLC25A20基因的纯合c.199-10T>G变体，都是从他的父母那里继承下来的.其中,c.106-2A>G和c.49G>C变体以前没有报道。根据美国医学遗传学和基因组学学院（ACMG）的指南，c.49G>C(p.Gly17Arg),c.106-2A>G，和c.199-10T>G变异被分类为可能致病(PM2_支持+PP3+PM3_strong+PP4)，致病性(PVS1+PM2_支持+PM5+PP3)，和致病性(PVS1+PM2_支持+PP3+PP5)，分别。
结论：结合其临床表型和基因分析，两名儿童均被诊断为CACTD.上述发现为他们的治疗以及家庭的遗传咨询和产前诊断提供了基础。
方法：选取分别于2018年1月3日和11月19日在甘肃省妇幼保健院确诊为CACTD的2例患儿作为研究对象。进行三全外显子组测序(trio-WES),和候选变异体通过Sanger测序和致病性分析进行验证。
结果：两名儿童均为男性，主要表现为低血糖。Trio-WES和Sanger测序显示，儿童1具有SLC25A20基因的复合杂合变体，即c.49G>C（p。Gly17Arg）和c.106-2A>G，从他的父亲和母亲那里继承下来，分别。儿童2具有SLC25A20基因的纯合c.199-10T>G变体，都是从他的父母那里继承下来的.其中,c.106-2A>G和c.49G>C变体以前没有报道。根据美国医学遗传学和基因组学学院（ACMG）的指南，c.49G>C(p.Gly17Arg),c.106-2A>G，和c.199-10T>G变异被分类为可能致病(PM2_支持+PP3+PM3_strong+PP4)，致病性(PVS1+PM2_支持+PM5+PP3)，和致病性(PVS1+PM2_支持+PP3+PP5)，分别。
结论：结合其临床表型和基因分析，两名儿童均被诊断为CACTD.上述发现为他们的治疗以及家庭的遗传咨询和产前诊断提供了基础。
