De Novo ABCD1 Gene Mutation in an Indian Patient With Adrenoleukodystrophy

• Published in: Pediatric neurology 2008-10, Vol.39 (4), p.289-292
• Main Authors: Kumar, Neeraj, MSc, Shukla, Pallavi, MSc, Taneja, Krishna K., PhD, Kalra, Veena, MD, Bansal, Surendra K., PhD
• Format: Article
• Language: English
• Subjects: Adrenoleukodystrophy - genetics; Adrenoleukodystrophy - pathology; ATP Binding Cassette Transporter, Sub-Family D, Member 1; ATP-Binding Cassette Transporters - genetics; Biological and medical sciences; Child; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; DNA Mutational Analysis; Humans; India; Male; Medical sciences; Mutation; Neurology; Pediatrics; Polymerase Chain Reaction
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2008.07.006

A large number of ABCD1 gene mutations have been reported all over the world, but not previously in India. We report on the first known patient with childhood cerebral adrenoleukodystrophy and a de novo 3′ splice-site mutation in this gene. Magnetic resonance imaging of the brain revealed large, confluent, hyperintense areas in the bilateral cerebral white matter, predominantly parieto-occipital, with extensions into posterior regions that led to breakdown of the blood-brain barrier. An increased level of very long chain fatty acids was also consistent with the biochemical defect for adrenoleukodystrophy. Sequencing of the ABCD1 gene of this patient identified a 3′ splice-site mutation in the intervening sequence 4 (−2a > g). We did not find any mutation in the gene of the proband's mother, which confirms its de novo occurrence.