skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes

Abstract

Recently, the gene for the most common peroxisomal disorder, X-linked adrenoleukodystrophy (X-ALD), has been described encoding a peroxisomal membrane transporter protein. We analyzed the entire protein-coding sequence of this gene by reverse-transcription PCR, SSCP, and DNA sequencing in five patients with different clinical expressions were cerebral childhood ALD, adrenomyecloneuropathy (AMN), and {open_quotes}Addison disease only{close_quotes} (AD) phenotype. In the three patients exhibiting the classical picture of severe childhood ALD we identified in the 5{prime} portion of the X-ALD gene a 38-bp deletion that causes a frameshift mutation, a 3-bp deletion leading to a deletion of an amino acid in the ATP-binding domain of the ALD protein, and a missense mutation. In the patient with the clinical phenotype of AMN, a nonsense mutation in codon 212, along with a second site mutation at codon 178, was observed. Analysis of the patient with the ADO phenotype revealed a further missense mutation at a highly conserved position in the ALDP/PMP70 comparison. The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD. Since themore » current biochemical techniques for X-ALD carrier detection in affected families lack sufficient reliability, our procedure described for systematic mutation scanning is also capable of improving genetic counseling and prenatal diagnosis. 19 refs., 6 figs., 3 tabs.« less

Authors:
; ; ; ; ;  [1];  [2];  [3];  [4]
  1. Univ. of Munich (Germany)
  2. Univ. of Graz (Germany)
  3. Univ. of Duesseldorf (Germany)
  4. Univ. of Bonn (Germany)
Publication Date:
OSTI Identifier:
70422
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Human Genetics; Journal Volume: 56; Journal Issue: 4; Other Information: PBD: Apr 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; POLYMERASE CHAIN REACTION; DNA SEQUENCING; GENE MUTATIONS; SCREENING; HUMAN X CHROMOSOME; CHROMOSOMAL ABERRATIONS; PROTEINS; MEMBRANE TRANSPORT; PATIENTS; NERVOUS SYSTEM DISEASES; HEREDITARY DISEASES; PHENOTYPE

Citation Formats

Braun, A., Ambach, H., Kammerer, S., Rolinski, B., Roscher, A., Rabl, W., Stoeckler, S., Gaertner, J., and Zierz, S. Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes. United States: N. p., 1995. Web.
Braun, A., Ambach, H., Kammerer, S., Rolinski, B., Roscher, A., Rabl, W., Stoeckler, S., Gaertner, J., & Zierz, S. Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes. United States.
Braun, A., Ambach, H., Kammerer, S., Rolinski, B., Roscher, A., Rabl, W., Stoeckler, S., Gaertner, J., and Zierz, S. Sat . "Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes". United States.
@article{osti_70422,
title = {Mutations in the gene for X-linked adrenoleukodystrophy in patients with different clinical phenotypes},
author = {Braun, A. and Ambach, H. and Kammerer, S. and Rolinski, B. and Roscher, A. and Rabl, W. and Stoeckler, S. and Gaertner, J. and Zierz, S.},
abstractNote = {Recently, the gene for the most common peroxisomal disorder, X-linked adrenoleukodystrophy (X-ALD), has been described encoding a peroxisomal membrane transporter protein. We analyzed the entire protein-coding sequence of this gene by reverse-transcription PCR, SSCP, and DNA sequencing in five patients with different clinical expressions were cerebral childhood ALD, adrenomyecloneuropathy (AMN), and {open_quotes}Addison disease only{close_quotes} (AD) phenotype. In the three patients exhibiting the classical picture of severe childhood ALD we identified in the 5{prime} portion of the X-ALD gene a 38-bp deletion that causes a frameshift mutation, a 3-bp deletion leading to a deletion of an amino acid in the ATP-binding domain of the ALD protein, and a missense mutation. In the patient with the clinical phenotype of AMN, a nonsense mutation in codon 212, along with a second site mutation at codon 178, was observed. Analysis of the patient with the ADO phenotype revealed a further missense mutation at a highly conserved position in the ALDP/PMP70 comparison. The disruptive nature of two mutations (i.e., the frameshift and the nonsense mutation) in patients with biochemically proved childhood ALD and AMN further strongly supports the hypothesis that alterations in this gene play a crucial role in the pathogenesis of X-ALD. Since the current biochemical techniques for X-ALD carrier detection in affected families lack sufficient reliability, our procedure described for systematic mutation scanning is also capable of improving genetic counseling and prenatal diagnosis. 19 refs., 6 figs., 3 tabs.},
doi = {},
journal = {American Journal of Human Genetics},
number = 4,
volume = 56,
place = {United States},
year = {Sat Apr 01 00:00:00 EST 1995},
month = {Sat Apr 01 00:00:00 EST 1995}
}