Genetics division, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), New Delhi 110029 India.
Clin Chim Acta. 2011 Nov 20;412(23-24):2289-95. doi: 10.1016/j.cca.2011.08.026. Epub 2011 Aug 26.
X-linked Adrenoleukodystrophy (X-ALD), with an incidence of 1:14,000 is the most frequent monogenic demyelinating disorder worldwide. The principal biochemical abnormality in X-ALD is the increased levels of saturated, unbranched very long chain fatty acids (VLCFA). It is caused by mutations in ABCD1 gene. No molecular data on X-ALD is available in India and mutational spectrum in Indian patients is not known.
We standardized conformation sensitive gel electrophoresis (CSGE) method to detect mutations in ABCD1 gene in twenty Indian patients with X-ALD. The results were confirmed by sequencing. Genotype-phenotype correlation was also attempted. Prenatal diagnosis (PND) in one family was done using chorionic villi (CV) sample at 12 weeks of gestation.
Out of twenty, causative mutations could be identified in twelve patients (60%). Six reported and four novel mutations were identified. Three polymorphisms were also observed. No hot spot was found. No significant genotype-phenotype correlation could be established.
The study identified the mutation spectrum of Indian X-ALD patients, which enabled us to offer accurate genetic counseling, carrier detection and prenatal diagnosis where needed.
X 连锁肾上腺脑白质营养不良（X-ALD）的发病率为 1:14000，是全球最常见的单基因脱髓鞘疾病。X-ALD 的主要生化异常是饱和、无支链的超长链脂肪酸（VLCFA）水平升高。它是由 ABCD1 基因突变引起的。印度尚无 X-ALD 的分子数据，印度患者的突变谱也不清楚。
我们将构象敏感凝胶电泳（CSGE）方法标准化，用于检测 20 名印度 X-ALD 患者的 ABCD1 基因突变。结果通过测序进行了确认。还尝试了基因型-表型相关性。通过对 12 周妊娠的绒毛膜（CV）样本进行了一个家系的产前诊断（PND）。
在 20 名患者中，有 12 名（60%）患者可以确定致病突变。发现了 6 种已报道的和 4 种新的突变。还观察到了 3 种多态性。未发现热点。未能建立显著的基因型-表型相关性。
该研究确定了印度 X-ALD 患者的突变谱，使我们能够提供准确的遗传咨询、携带者检测和有需要时的产前诊断。
