中国人多种羧化酶缺陷症患儿4例及其父母基因突变分析  

Gene mutation analysis in four Chinese patients with multiple carboxylase deficiency

作　　者：李端[1] 刘丽[1] 李秀珍[1] 程静[1] 赵小媛[1] 周荣[1] 

机构地区：[1]广州市儿童医院内分泌代谢科,510120

出　　处：《中华儿科杂志》2006年第11期865-868,共4页Chinese Journal of Pediatrics

基　　金：973国家重点基础研究发展规划项目(2001CB510306);广东省科技厅计划项目(2004B36001040)

摘　　要：目的研究中国人多种羧化酶缺陷症(multiple carboxylase deficiency,MCD)患儿及其父母基因突变情况。方法应用聚合酶链反应-直接测序的方法,对4例临床确诊MCD的中国患儿的生物素酶(BT)基因和全羧化酶合成酶(HLCS)基因的各个外显子及其两侧侧翼序列进行突变的检测,并对其父母进行相应突变基因检测。结果4例患儿皆为HLCS基因突变,没有发现BT基因突变。共发现1个缺失突变:780delG,3个错义突变:1522C>T(R508W)、1367A>G(Y456C)和1900G>A(D634N)。例1为HLCS基因的第11号外显子上的1522C>T的错义突变,为纯合突变;例2为第11号外显子的1522C>T和第9号外显子的1367A>G的复合性杂合突变;例3为第11号外显子的1522C>T和第13号外显子的1900G>A的复合性杂合突变;例4为第11号外显子的1522C>T和第7号外显子的780delG的复合性杂合突变;4例患儿的父母均是突变基因携带者。结论R508W突变可能是中国MCD中HLCS缺陷患儿较常见的突变。Objective Multiple carboxylase deficiency MCD ） is an autosomal recessive disorder. MCD is characterized by skin rash, metabolic acidosis, vomiting and psychomotor retardation. Depending on deficiency of the enzyme, MCD includes two different forms, biotinidase deficiency （BTD, OMIM 253260 ） and holocarboxylase synthetase deficiency （HLCSD, OMIM 253270 ）. In this study, we analyzed gene mutations of four Chinese MCD patients and to explore the mutation spectrum and possibility of a molecular diagnosis. Methods All exons and their flanking introns of biotinidase gene and HLCS gene were screened by polymerase chain reaction combined with DNA direct sequencing in four Chinese MCD patients. Genomic DNA was extracted using a kit from the peripheral blood leukocytes of each patient. PCR amplification products were checked by 2% agarose gel electrophoresis and were subsequently sequenced with both the forward and reverse primers. Results All patients showed mutations in HLCS gene, whereas no mutation was found in biotinidase gene, proving that all the four patients had HLCS deficiency. Four previously reported mutations in HLCS gene were detected （Y456C, R508W, D634N and 780delG）. A missense mutation of 1522C 〉 T in exon 11 of HLCS gene, which was a homozygotic mutation, was identified in patient 1 ; a mutation of 1522C 〉T in exon 11 combined with a mutation of 1367A 〉 G in exon 9, which was a compound heterozygotic mutation, was identified in patient 2; a mutation of 1522C 〉 T in exon 11 combined with a mutation of 1900G 〉 A in exon 13, which was a compound heterozygotic mutation, was identified in patient 3 ; a mutation of 1522C 〉 T in exon 11 combined with a mutation of 780delG in exon 7, which was a compound heterozygotic mutation, was identified in patient 4. All the parents were carriers of mutations. No additional carrier of this four mutations was identified from 50 samples of Chinese controls. Conclusion The 1522C 〉 T （R508W） mutation probably represents a mutational hot-spot in

关 键 词：多源性羧化酶缺乏 碳氮连接酶类 生物素酶 突变 

分 类 号：R725.8[医药卫生—儿科]