摘要
目的 检测肾上腺脑白质营养不良 (adrenoleukodystrophy,AL D) (MIM 3 0 0 10 0 )患者编码AL D蛋白的 ABCD1基因 [ATP-结合盒 (ATP-binding cassette,ABC)超家族中 D亚家族 1]突变。方法 提取无亲缘关系的 14例中国 AL D患者及其中 2例患者父母基因组 DNA,聚合酶链反应 (polymerasechain reaction,PCR)扩增 ABCD1基因的第 6外显子 ,以琼脂糖凝胶电泳鉴定 PCR产物 ,PCR产物纯化后DNA直接测序。结果 证实 3个患者的 ABCD1基因第 6外显子有突变 ,其中 1例患者为 5′末端上游第 6个碱基 C缺失 (14 89-6del C) ,推测该突变可能导致剪切错误 ;1例患者为错义突变 1559T→ A(L52 0 Q) ,这两例患者的母亲均为杂合突变。另 1例患者为 1548G→ A(L516L)的同义突变。结论 首次报告了中国大陆 AL D患者 ABCD1基因突变。第 6外显子无大片段缺失和重组突变。同一血缘族中可有不同的表型存在 ,提示是否有其它遗传或环境因素参与表型的表达。通过 DNA测序方法亦证实其中 2例患者之母为ABCD1基因的杂合子。
Objective: To detect the mutations in exon 6 of ABCD1 gene encoding adrenoleukodystrophy protein (ALDP) in Chinese X-linked adrenoleukodystrophy (ALD, MIM 300100) patients. Methods: Genomic DNA from 14 unrelated patients and two patients' parents with X-linked ALD was extracted using standard procedures from the peripheral blood leukocytes. Polymerase chain reaction (PCR) and DNA direct sequencing were employed to analyze exon 6 of ABCD1 gene. Results: Three mutations in exon 6 were identified in 3 of 14 patients. One mutation was deleted 1 base pair at splice acceptor-site (1489-6 del C). It was not clear what the effect of this mutation is on the ALD protein, maybe induce splicing error. One missense mutation: T1559A (L520Q). These two patients' mothers were heterozygous. The third patient had a mutation: G1548A (L516 L), which is a known polymorphism. It was not a disease causing mutation, so there should be another mutation in this patient. Conclusion: For the first time, mutations in ABCD1 are identified in Chinese ALD patients in the mainland of China. No major gene deletion or rearrangement is detected in exon 6. Despite many mutations having been identified in patients with these clinical phenotypes, the genotype-phenotype correlations have not been clarified, suggesting that other genetic or environmental factors may also be involved in determining phenotypic expression in ALD. Two carriers are also confirmed.
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2003年第5期400-403,共4页
Chinese Journal of Medical Genetics
