Wang Zhihong, Ke Longfeng, Yan Aizhen, Zhu Zhongyong, Lan Fenghua
Research Center for Molecular Diagnosis of Genetic Diseases, Fuzhou General Hospital, Fuzhou, PR China.
Clin Chem Lab Med. 2008;46(12):1702-6. doi: 10.1515/CCLM.2008.331.
Mutations in the ABCD1 gene lead to X-linked adrenoleukodystrophy, a neurodegenerative disorder. Hundreds of hereditary mutations of the gene have been reported in patients with X-linked adrenoleukodystrophy, but there have been no reports of de novo mutations.
The coding region of ABCD1 cDNA of two patients was amplified and sequenced. To confirm the mutations in the ABCD1 gene of the patients and screen for mutations in their family members, the genomic DNA was analyzed by direct sequencing and denaturing high performance liquid chromatography.
Two missense mutations (C631Y and G512S) were identified in the probands, but the mutations were not found in their parents. Tests for paternity identification excluded the possibility of misparentage.
The mutations identified in the two male patients were de novo mutations. Mutation analysis of parents of the proband may be helpful for pregnancy planning and evaluation of the recurrence risk to siblings of the proband.
ABCD1基因突变会导致X连锁肾上腺脑白质营养不良，这是一种神经退行性疾病。在X连锁肾上腺脑白质营养不良患者中已报道了该基因的数百种遗传性突变，但尚未有新发突变的报道。
对两名患者的ABCD1 cDNA编码区进行扩增和测序。为确认患者ABCD1基因中的突变并筛查其家庭成员中的突变，采用直接测序和变性高效液相色谱法分析基因组DNA。
在先证者中鉴定出两个错义突变（C631Y和G512S），但在其父母中未发现这些突变。亲子鉴定测试排除了亲子关系错误的可能性。
在两名男性患者中鉴定出的突变是新发突变。先证者父母的突变分析可能有助于妊娠计划和评估先证者兄弟姐妹的复发风险。
