NM_000033.4(ABCD1):c.871GAG[1] (p.Glu292del) AND Adrenoleukodystrophy

Clinical significance:Pathogenic (Last evaluated: Sep 11, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000012066.11

Allele description [Variation Report for NM_000033.4(ABCD1):c.871GAG[1] (p.Glu292del)]

NM_000033.4(ABCD1):c.871GAG[1] (p.Glu292del)

Gene:
ABCD1:ATP binding cassette subfamily D member 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
Xq28
Genomic location:
Preferred name:
NM_000033.4(ABCD1):c.871GAG[1] (p.Glu292del)
Other names:
E291del
HGVS:
  • NC_000023.11:g.153726137GAG[1]
  • NG_009022.2:g.6270GAG[1]
  • NG_023231.1:g.3606TCC[1]
  • NM_000033.4:c.871GAG[1]MANE SELECT
  • NP_000024.2:p.Glu292del
  • LRG_1017t1:c.871GAG[1]
  • LRG_1017:g.6270GAG[1]
  • LRG_1017p1:p.Glu292del
  • NC_000023.10:g.152991592GAG[1]
  • NM_000033.4:c.874_876delGAGMANE SELECT
  • NP_000024.2:p.Glu291del
Protein change:
E292del; GLU291DEL
Links:
OMIM: 300371.0023; dbSNP: rs387906496
NCBI 1000 Genomes Browser:
rs387906496
Molecular consequence:
  • NM_000033.4:c.871GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:
Adrenoleukodystrophy (ALD)
Synonyms:
ADDISON DISEASE AND CEREBRAL SCLEROSIS; BRONZE SCHILDER DISEASE; MELANODERMIC LEUKODYSTROPHY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018544; MedGen: C0162309; OMIM: 300100

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000032300OMIMno assertion criteria providedPathogenic
(Jun 30, 1998)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV001167277Johns Hopkins Genomics, Johns Hopkins Universitycriteria provided, single submitter
Pathogenic
(Sep 11, 2019)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A Japanese family with adrenoleukodystrophy with a codon 291 deletion: a clinical, biochemical, pathological, and genetic report.

Kano S, Watanabe M, Kanai M, Koike R, Onodera O, Tsuji S, Okamoto K, Shoji M.

J Neurol Sci. 1998 Jun 30;158(2):187-92.

PubMed [citation]
PMID:
9702690

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From OMIM, SCV000032300.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

The glu291-to-lys mutation of the ALD gene (300371.0001) is a recognized cause of adrenoleukodystrophy (300100). Kano et al. (1998) described deletion of codon 291 (GAG) in a Japanese family with a variety of phenotypes in affected individuals. Whereas the proband was classified as having a rare intermediate type of adult cerebral and cerebello-brainstem form of ALD, his younger brother and nephew had the childhood type of ALD. Another nephew was classified as having an adolescent form. At 47 years of age, the proband developed depression, personality change, forgetfulness, and carelessness. He was noted to be severely amotivational, apathetic, and irritable. These behavioral abnormalities resulted in occupational and social compromise and hospitalization at age 48. No skin pigmentation was noted. The level of tau (157140) in the proband's cerebrospinal fluid was as high as that of patients with Alzheimer disease (104300). His brain magnetic resonance image showed bilateral abnormalities in the cerebellar hemispheres and brainstem, but not in the cerebral white matter, where marked reductions of cerebral blood flow and oxygen metabolism were clearly demonstrated by positron emission tomography. The proband's younger brother developed mental deterioration, inactiveness, impaired vision, slurring of speech, and gait disturbance at age 8. He died 1 year later of respiratory failure. Autopsy was performed in his case and in that of one of the nephews, who had onset of symptoms at age 7 and died at age 9. Autopsy in both showed massive demyelination of the cerebral white matter but sparing of the U-fibers, compatible with childhood ALD.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Johns Hopkins Genomics, Johns Hopkins University, SCV001167277.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 28, 2021

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