title: Identification of seven novel mutations in ABCD1 by a DHPLC-based assay in Italian patients with X-linked adrenoleukodystrophy.
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.
authors.affiliation: Molecular Medicine and Endocrinology, IRCCS Bambino Gesù Children's Hospital, Rome.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Montagna
authors.forename: Antonella
authors.initials: A
authors.lastname: Di Biase
authors.forename: Marco
authors.initials: M
authors.lastname: Cappa
authors.forename: Mariarosa A B
authors.initials: MA
authors.lastname: Melone
authors.forename: Carlo
authors.initials: C
authors.lastname: Piantadosi
authors.forename: Diego
authors.initials: D
authors.lastname: Colabianchi
authors.forename: Clarice
authors.initials: C
authors.lastname: Patrono
authors.forename: Lucilla
authors.initials: L
authors.lastname: Attori
authors.forename: Natalia
authors.initials: N
authors.lastname: Cannelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Cotrufo
authors.forename: Serafina
authors.initials: S
authors.lastname: Salvati
authors.forename: Filippo M
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000326:Adrenoleukodystrophy / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation
chemical_list: C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters