Molecular Analysis of ABCD1 Gene in Indian Patients With X-linked Adrenoleukodystrophy

Clin Chim Acta. 2011 Nov 20;412(23-24):2289-95. doi: 10.1016/j.cca.2011.08.026. Epub 2011 Aug 26.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • Adrenoleukodystrophy / diagnosis
  • Adrenoleukodystrophy / genetics*
  • Female
  • Humans
  • India
  • Pregnancy
  • Prenatal Diagnosis

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters