Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E

A novel neonatal phenotype similar to peroxisomal biogenesis disorders

Deyanira Corzo, William Gibson, Kisha Johnson, Grant Mitchell, Guy LePage, Gerald F. Cox, Robin Casey, Carolyn Zeiss, Heidi Tyson, Garry R. Cutting, Gerald Raymond, Kirby D. Smith, Paul A. Watkins, Ann B. Moser, Hugo W. Moser, Steven J. Steinberg

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette-transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 ± 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal β-oxidation pathway - disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency - also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term "contiguous ABCD1 DXS1357E deletion syndrome" (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED.

Original languageEnglish (US)
Pages (from-to)1520-1531
Number of pages12
JournalAmerican Journal of Human Genetics
Volume70
Issue number6
DOIs
StatePublished - Jan 1 2002

Fingerprint

Peroxisomal Disorders
Adrenoleukodystrophy
X-Linked Genes
Phenotype
Mutation
Genetic Promoter Regions
Enzymes
Fatty Acids
Acyl-CoA Oxidase
Protein Deficiency
ATP-Binding Cassette Transporters
Genetic Counseling
Diagnostic Errors
Age of Onset
Genes
Membrane Proteins
Proteins
Carbon
Biomarkers
Newborn Infant

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Corzo, Deyanira ; Gibson, William ; Johnson, Kisha ; Mitchell, Grant ; LePage, Guy ; Cox, Gerald F. ; Casey, Robin ; Zeiss, Carolyn ; Tyson, Heidi ; Cutting, Garry R. ; Raymond, Gerald ; Smith, Kirby D. ; Watkins, Paul A. ; Moser, Ann B. ; Moser, Hugo W. ; Steinberg, Steven J. / Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E : A novel neonatal phenotype similar to peroxisomal biogenesis disorders. In: American Journal of Human Genetics. 2002 ; Vol. 70, No. 6. pp. 1520-1531.
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title = "Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: A novel neonatal phenotype similar to peroxisomal biogenesis disorders",
abstract = "X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette-transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 ± 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal β-oxidation pathway - disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency - also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term {"}contiguous ABCD1 DXS1357E deletion syndrome{"} (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED.",
author = "Deyanira Corzo and William Gibson and Kisha Johnson and Grant Mitchell and Guy LePage and Cox, {Gerald F.} and Robin Casey and Carolyn Zeiss and Heidi Tyson and Cutting, {Garry R.} and Gerald Raymond and Smith, {Kirby D.} and Watkins, {Paul A.} and Moser, {Ann B.} and Moser, {Hugo W.} and Steinberg, {Steven J.}",
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Corzo, D, Gibson, W, Johnson, K, Mitchell, G, LePage, G, Cox, GF, Casey, R, Zeiss, C, Tyson, H, Cutting, GR, Raymond, G, Smith, KD, Watkins, PA, Moser, AB, Moser, HW & Steinberg, SJ 2002, 'Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E: A novel neonatal phenotype similar to peroxisomal biogenesis disorders', American Journal of Human Genetics, vol. 70, no. 6, pp. 1520-1531. https://doi.org/10.1086/340849

Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E : A novel neonatal phenotype similar to peroxisomal biogenesis disorders. / Corzo, Deyanira; Gibson, William; Johnson, Kisha; Mitchell, Grant; LePage, Guy; Cox, Gerald F.; Casey, Robin; Zeiss, Carolyn; Tyson, Heidi; Cutting, Garry R.; Raymond, Gerald; Smith, Kirby D.; Watkins, Paul A.; Moser, Ann B.; Moser, Hugo W.; Steinberg, Steven J.

In: American Journal of Human Genetics, Vol. 70, No. 6, 01.01.2002, p. 1520-1531.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Contiguous deletion of the X-linked adrenoleukodystrophy gene (ABCD1) and DXS1357E

T2 - A novel neonatal phenotype similar to peroxisomal biogenesis disorders

AU - Corzo, Deyanira

AU - Gibson, William

AU - Johnson, Kisha

AU - Mitchell, Grant

AU - LePage, Guy

AU - Cox, Gerald F.

AU - Casey, Robin

AU - Zeiss, Carolyn

AU - Tyson, Heidi

AU - Cutting, Garry R.

AU - Raymond, Gerald

AU - Smith, Kirby D.

AU - Watkins, Paul A.

AU - Moser, Ann B.

AU - Moser, Hugo W.

AU - Steinberg, Steven J.

PY - 2002/1/1

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N2 - X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette-transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 ± 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal β-oxidation pathway - disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency - also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term "contiguous ABCD1 DXS1357E deletion syndrome" (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED.

AB - X-linked adrenoleukodystrophy (X-ALD) results from mutations in ABCD1. ABCD1 resides on Xq28 and encodes an integral peroxisomal membrane protein (ALD protein [ALDP]) that is of unknown function and that belongs to the ATP-binding cassette-transporter superfamily. Individuals with ABCD1 mutations accumulate very-long-chain fatty acids (VLCFA) (carbon length >22). Childhood cerebral X-ALD is the most devastating form of the disease. These children have the earliest onset (age 7.2 ± 1.7 years) among the clinical phenotypes for ABCD1 mutations, but onset does not occur at <3 years of age. Individuals with either peroxisomal biogenesis disorders (PBD) or single-enzyme deficiencies (SED) in the peroxisomal β-oxidation pathway - disorders such as acyl CoA oxidase deficiency and bifunctional protein deficiency - also accumulate VLCFA, but they present during the neonatal period. Until now, it has been possible to distinguish unequivocally between individuals with these autosomal recessively inherited syndromes and individuals with ABCD1 mutations, on the basis of the clinical presentation and measurement of other biochemical markers. We have identified three newborn boys who had clinical symptoms and initial biochemical results consistent with PBD or SED. In further study, however, we showed that they lacked ALDP, and we identified deletions that extended into the promoter region of ABCD1 and the neighboring gene, DXS1357E. Mutations in DXS1357E and the ABCD1 promoter region have not been described previously. We propose that the term "contiguous ABCD1 DXS1357E deletion syndrome" (CADDS) be used to identify this new contiguous-gene syndrome. The three patients with CADDS who are described here have important implications for genetic counseling, because individuals with CADDS may previously have been misdiagnosed as having an autosomal recessive PBD or SED.

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