Two Novel Multiple Mutations in Chinese Patients with Adrenoleukodystrophy

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene. Up to now, more than 1 050 mutations have been reported in the ABCD1 gene, of which only 10 are multiple mutations in one allele of the gene. In this study, we report 2 novel multiple mutations in 2 patients with X-ALD from 2 unrelated Chinese families. Total RNA and genomic DNA were isolated from peripheral blood of the 2 patients, and the ABCD1 gene was analyzed by direct sequencing and denaturing high-performance liquid chromatography. We detected [p.Ser108X+p.Arg259Trp] in patient 1, [p.Lys217Glu+p.Val489Val] in patient 2 in one allele of the ABCD1 gene. Both novel multiple mutations have not previously been reported and this is the first report of multiple mutations identified in Chinese patients with X-ALD.

Key words

ABCD1 gene - multiple mutations - molecular diagnosis - X-linked adrenoleukodystrophy

References

• 1 Cartier N, Hacein-Bey-Abina S, Bartholomae  CC. et al . Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy.  Science. 2009;  326 818-823
• 2 Dvorakova L, Storkanova G, Unterrainer G. et al . Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange.  Hum Mutat. 2001;  18 52-60
• 3 Gartner J, Dehmel T, Klusmann A. et al . Functional characterization of the adrenoleukodystrophy protein (ALDP) and disease pathogenesis.  Endoc Res. 2002;  28 741-748
• 4 Hugo W, Moser HW, Raymond GV. et al . Adrenoleukodystrophy: new approaches to a neurodegenerative disease.  JAMA. 2005;  294 3131-3134
• 5 Kemp S, Pujol A, Waterham HR. et al . ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations.  Hum Mutat. 2001;  18 499-515
• 6 Lan FH, Yang BS, Wu YB. et al . Molecular diagnosis of adrenoleukodystrophy.  Fujian Med J. 2003;  25 39-42
• 7 Montagna G, Di Biase A, Cappa M. et al . Identification of seven novel mutations in ABCD1 by a DHPLC-based assay in Italian patients with X-linked adrenoleukodystrophy.  Hum Mutat. 2005;  25 222-227
• 8 Moser HW. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy.  Brain. 1997;  120 1485-1508

Correspondence