Identification of Seven Novel Mutations in ABCD1 by a DHPLC-based Assay in Italian Patients With X-linked Adrenoleukodystrophy

Hum Mutat. 2005 Feb;25(2):222. doi: 10.1002/humu.9303.

Abstract

We report the molecular findings in 14 patients (12 families) with X-linked adrenoleukodystrophy (X-ALD, MIM# 300100), a well-defined peroxisomal disorder attributed to mutations in the ABCD1 gene on chromosome Xq28. With the aims of determining the spectrum of mutations and developing an efficient molecular genetic test for analysis of at-risk women whose carrier status is unknown, and to offer molecular confirmation of their status to obligate heterozygotes, regardless of their clinical status, we carried out molecular screening by setting up a denaturing high-performance liquid chromatography (DHPLC)-based protocol. We identified eleven hemizygous base changes in ABCD1, including seven new mutations (c.145underscore;146ins4, c.264C>G, c.919C>T, c.994C>T, c.1027G>A, c.1508T>C, and c.1540A>C, resulting in the p.Pro193fs, p.Cys88Trp, p.Gln307X, p.Gln332X, p.Gly343Ser, p.Leu503Pro, and p.Ser514Arg changes, respectively). Adding new variants to the repertoire of ABCD1 mutations in X-ALD, our data provide an efficient, cost-effective, and reliable DHPLC detection protocol for mutation screening of X-ALD families.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Adrenoleukodystrophy / diagnosis
  • Adrenoleukodystrophy / genetics*
  • Adrenoleukodystrophy / metabolism
  • Chromatography, High Pressure Liquid / methods
  • DNA Mutational Analysis / methods*
  • Female
  • Humans
  • Italy
  • Male
  • Mutation*

Substances

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

Associated data

  • OMIM/300100