Two intronic mutations in the adrenoleukodystrophy gene

Kemp, Stephan; Ligtenberg, M. J. L.; Geel, Björn M. van; Barth, Peter; Sarde, Claude-Olivier; Oost, B.A. van; Bolhuis, P. A.

doi:10.1002/humu.1380060316

Cited by 14 publications

(6 citation statements)

References 6 publications

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“…Although more than 50 variants in introns of ABCD1 have been reported to be pathogenic, the effects of the variants on the mRNA expression have been investigated in only a few patients. Indeed, to our knowledge, there have been only six previous studies in which an RT PCR analysis was conducted on patients carrying variants at splice sites (17,(19)(20)(21)(22)(23). The present and those previous reports all showed exon skipping or intron inclusion caused by aberrant splicing.…”

Section: B: the Results Of A Quantitative Analysis Using Lymphoblasto...supporting

confidence: 45%

Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in <i>ABCD1</i>

et al. 2024

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Adrenomyeloneuropathy (AMN)/adrenoleukodystrophy (ALD) is an X-linked genetic disorder caused by pathogenic variants in ABCD1. We treated a 54-year-old man with slowly progressive spastic paraparesis with later development of the cerebral form. A pathogenic splice-site variant of ABCD1 (c.1489-1G>A, p. Val497 Alafs*51) and elevated levels of very long-chain fatty acids were found, leading to the diagnosis of AMN. Detailed ABCD1 mRNA expression analyses revealed decreased levels of ABCD1 mRNA accompanied by deletion of the first 31 bp in exon 6. The altered mRNA transcriptional patterns associated with splice site variants are diverse and may provide important insights into ALD pathogenesis.

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Section: B: the Results Of A Quantitative Analysis Using Lymphoblasto...supporting

confidence: 45%

Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in <i>ABCD1</i>

et al. 2024

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“…Immunocytochemical studies (11)(12)(13) demonstrated that the X-ALD gene product (adrenoleukodystrophy protein; ALDP) is a peroxisomal membrane protein consistent with the observed biochemical abnormality in X-ALD patients. Mutational analyses of the X-ALD gene (9,(13)(14)(15)(16)(17) revealed the existence of mutations in all X-ALD patients examined, and complementation studies (18) showed that expression of ALDP restores ␤-oxidation of VLCFAs in patients' fibroblasts. While all evidence strongly supports the conclusion that the abnormality in ALDP results in X-ALD, its function is still unknown.…”

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confidence: 99%

A mouse model for X-linked adrenoleukodystrophy

Lawler

Watkins

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

265

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“…This proportion is similar to that observed in our study. The most common mutation is p.Gln472Argfs * 83 in exon 5 (25). Our 6 patients also mainly had missense mutations; however, none were common mutations.…”

Section: Discussionmentioning

confidence: 66%

The etiology and clinical features of non-CAH primary adrenal insufficiency in children

Liu

Kang

et al. 2022

Front. Pediatr.

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BackgroundThe most common cause of primary adrenal insufficiency (PAI) in children is congenital adrenal hyperplasia; however, other genetic causes occur. There is limited epidemiological and clinical information regarding non-CAH PAI.MethodsData for patients diagnosed from January 2015 to December 2021 at a tertiary hospital in northern China were retrospectively analyzed. We excluded those with CAH, which is the most common pathogenic disease among PAI patients. Next-generation sequencing was used for genetic analysis.ResultsThis retrospective study included 16 children (14 males and 2 females) with PAI. A genetic diagnosis was obtained for 14/16 (87.5%) individuals. Pathogenic variants occurred in 6 genes, including ABCD1 (6/16, 37.5%), NR0B1 (4/16, 25.0%), NR5A1/steroidogenic factor-1 (2/16; 12.5%), AAAS (1/16, 6.25%), and NNT (1/16, 6.25%). No genetic cause of PAI diagnosis was found in 2 girls (2/16, 12.5%).ConclusionsCauses of PAI in children are diverse and predominantly affect males. Most PAI in children is congenital, and ABCD1 gene defects account for the largest proportion of PAI cases. Whole-exome sequencing is a tool for diagnosis. However, diagnoses are unclear in some cases.

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Two intronic mutations in the adrenoleukodystrophy gene

Cited by 14 publications

References 6 publications

Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in <i>ABCD1</i>

Adrenomyeloneuropathy with Later Development of Cerebral Form Caused by a Hemizygous Splice-site Variant in <i>ABCD1</i>

A mouse model for X-linked adrenoleukodystrophy

The etiology and clinical features of non-CAH primary adrenal insufficiency in children

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