Abstract:
:An extremely rare pellagra-like condition has been described, which was partially responsive to niacin and associated with a multisystem involvement. The condition was proposed to represent a novel autosomal recessive entity but the underlying mutation remained unknown for almost three decades. The objective of this study was to identify the causal mutation in the pellagra-like condition and investigate the mechanism by which niacin confers clinical benefit. Autozygosity mapping and exome sequencing were used to identify the causal mutation, and comet assay on patient fibroblasts before and after niacin treatment to assess its effect on DNA damage. We identified a single disease locus that harbors a novel mutation in ERCC5, thus confirming that the condition is in fact xeroderma pigmentosum/Cockayne syndrome (XP/CS) complex. Importantly, we also show that the previously described dermatological response to niacin is consistent with a dramatic protective effect against ultraviolet-induced DNA damage in patient fibroblasts conferred by niacin treatment. Our findings show the power of exome sequencing in reassigning previously described novel clinical entities, and suggest a mechanism for the dermatological response to niacin in patients with XP/CS complex. This raises interesting possibilities about the potential therapeutic use of niacin in XP.
journal_name
Clin Genetjournal_title
Clinical geneticsauthors
Hijazi H,Salih MA,Hamad MH,Hassan HH,Salih SB,Mohamed KA,Mukhtar MM,Karrar ZA,Ansari S,Ibrahim N,Alkuraya FSdoi
10.1111/cge.12325subject
Has Abstractpub_date
2015-01-01 00:00:00pages
56-61issue
1eissn
0009-9163issn
1399-0004journal_volume
87pub_type
杂志文章abstract::We describe a family in which three sibs are compound heterozygotes for two rather rare CFTR splice-site mutations, the 621 + 1G-->T and the 711 + 1G-->T mutations. Little phenotypic variation was observed between sibs, of whom two are deceased. Their disease is characterized by pancreatic insufficiency, a severe pulm...
journal_title:Clinical genetics
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journal_title:Clinical genetics
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journal_title:Clinical genetics
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journal_title:Clinical genetics
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doi:10.1034/j.1399-0004.2002.620411.x
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1978.tb02100.x
更新日期:1978-12-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12194
更新日期:2014-05-01 00:00:00
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journal_title:Clinical genetics
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更新日期:1993-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-0004.2011.01747.x
更新日期:2012-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/cge.13217
更新日期:2018-05-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1981.tb00728.x
更新日期:1981-05-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1995.tb03957.x
更新日期:1995-04-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2011-03-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb03751.x
更新日期:1998-11-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章,评审
doi:10.1111/cge.13717
更新日期:2020-06-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1994.tb04024.x
更新日期:1994-04-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/cge.12985
更新日期:2017-08-01 00:00:00
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doi:10.1111/j.1399-0004.2007.00903.x
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:
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更新日期:2004-11-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
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更新日期:2013-05-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-0004.1986.tb00609.x
更新日期:1986-10-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1998.tb03693.x
更新日期:1998-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1976.tb01580.x
更新日期:1976-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-0004.1982.tb01443.x
更新日期:1982-11-01 00:00:00
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更新日期:2001-07-01 00:00:00
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journal_title:Clinical genetics
pub_type: 杂志文章
doi:10.1111/j.1399-0004.1993.tb04439.x
更新日期:1993-03-01 00:00:00
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journal_title:Clinical genetics
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doi:10.1111/j.1399-0004.2008.01039.x
更新日期:2008-12-01 00:00:00