Confirmation by Exome Sequencing of the Pathogenic Role of NCSTN Mutations in Acne Inversa (Hidradenitis Suppurativa)

1] Department of Dermatology, Institute of Dermatology, No. 1 Hospital, Anhui Medical University, Anhui, China [2] State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Anhui, China [3] These authors contributed equally to this work.
Journal of Investigative Dermatology (Impact Factor: 7.22). 03/2011; 131(7):1570-2. DOI: 10.1038/jid.2011.62
Source: PubMed


Abbreviations: AI, acne inversa

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    • "Nicastin itself has no catalytic activity. Recently, nicastrin mutations have been detected in Chinese[16–18] and French families with AI.[19] Mutations of the sonic hedgehog pathway could not be identified in AI patients.[20] "
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    ABSTRACT: Acne inversa (AI) is a disabilitating chronic inflammatory disease with major negative impact on quality of life and significant co-morbidities. This is an important link to insights into immune dysfunction, which stimulated therapeutic approaches like tumor necrosis-α inhibitor therapy. This new off-label drug treatment is particularly beneficial when used in combination with wide excision of inflamed skin and subcutaneous tissue. Retinoids have been reported to be helpful in secondary prevention. The standard of therapy in advanced cases is surgery with wide excisions and healing by secondary intention. This treatment results in significant reduction of complaints and achieves satisfactory body contouring.
    03/2013; 4(1):2-11. DOI:10.4103/2229-5178.105454
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    • "Recently, exome sequencing (also known as targeted exome capture) was demonstrated to be a cheaper but efficient strategy to selectively sequence the whole genome coding regions. It has been widely used to identify genes for rare monogenic diseases and can also provide molecular identification of Mendelian diseases when the clinical diagnosis is uncertain.6–9 Here, we identified a novel causative gene for MUHH by combining exome sequencing with the linkage information from our previous study.3 "
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    ABSTRACT: Background Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1–1q21.3 region responsible for MUHH has been identified. Methods Exome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1–1q21.3. Results We identified a missense mutation in EPS8L3 (NM_024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1–1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group. Conclusions Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes.
    Journal of Medical Genetics 10/2012; 49(12). DOI:10.1136/jmedgenet-2012-101134 · 6.34 Impact Factor
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    • "By combining the mapping and sequencing data, a sequence variant in RPL21, encoding the ribosomal protein L21, was shown to underlie the disease (Zhou et al., 2011). Additional examples of the use of NGS in investigative dermatology include two recent confirmatory studies implicating genes encoding components of g-secretase in acne inversa (Liu et al., 2011; Pink et al., 2011); the discovery of the gene associated with terminal osseous "
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    ABSTRACT: The past two decades have seen significant and unprecedented progress in human genetics owing to the advent of novel molecular biological technologies and major developments in computational methods. Dermatology has benefited from and, in some cases, led these advances. In this article, we review major discoveries in the field of inherited hair diseases, which illustrate the changes that genodermatology has undergone in recent years from a mostly descriptive discipline through the elucidation of the molecular basis of numerous disorders, up to the first attempts at translating these new findings into novel preventive and therapeutic tools to the benefit of our patients.
    Journal of Investigative Dermatology 12/2011; 132(3 Pt 2):906-14. DOI:10.1038/jid.2011.408 · 7.22 Impact Factor
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