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Identification of a genetic locus for autosomal dominant disseminated superficial actinic porokeratosis on chromosome 1p31.3–p31.1

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Abstract

Disseminated superficial actinic porokeratosis (DSAP) is a chronic autosomal dominant cutaneous disorder with high genetic heterogeneity. Two genetic loci for DSAP were identified, but no specific genes were reported to date. The pathogenic mechanism of this disorder remains to be elucidated. In this study, a large, five-generation Chinese family with DSAP was genetically characterized. Two known DSAP loci, DSAP1 and DSAP2, two DSAP candidate genes (SART3 and SSH1), one DSP-linked locus and one PPPD-linked locus were first excluded in the family. The family was then characterized by genome-wide linkage analysis and a new DSAP locus was identified on chromosome 1p31.3–p31.1 with a maximum two-point LOD score of 5.09 with marker D1S2897 (θ = 0). Fine mapping showed that the disease gene was located within an 8.2 cM or 11.9 Mb region between markers D1S438 and D1S464. This is the third locus identified for DSAP (DSAP3). Eight candidate genes including GNG12, IL12RB2, ITGB3BP, DNAJ6, PIN1L, GADD45A, RPE65 and NEGR1 were sequenced, but found to be negative for functional sequence variants. Further mutational analysis of the candidate genes in the region will identify the specific gene for DSAP, which will provide insights into the pathogenesis of DSAP.

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Abbreviations

DSAP:

Disseminated superficial actinic porokeratosis

PCR:

Polymerase chain reaction

LOD:

Logarithm of odds ratio

SNP:

Single nucleotide polymorphism

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Acknowledgments

We thank the patients and families for their enthusiastic participation. This study was supported by the China Natural Science Foundation grant 30571677(ML), 30670857 (QKW), and the Chinese Ministry of Science and Technology 863 Project grant No. 2006AA02Z476 (QKW). Q. K. Wang is an Established Investigator of the American Heart Association (0440157N).

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Authors and Affiliations

  1. Key Laboratory of Molecular Biophysics of Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

    Ping Liu, Qi Yao, Xu Wang, Xinyuan Huang, Pengyun Wang, Mingxiong Yuan, Jing Yu Liu, Qing K. Wang & Mugen Liu

  2. Union Hospital, Huazhong University of Science and Technology, Wuhan, China

    Shouyan Zhang, Xiangyang Liu & Changzheng Huang

  3. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA

    Qing K. Wang

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  1. Ping Liu
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  2. Shouyan Zhang
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  3. Qi Yao
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  4. Xiangyang Liu
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  5. Xu Wang
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  7. Xinyuan Huang
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  8. Pengyun Wang
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  9. Mingxiong Yuan
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  10. Jing Yu Liu
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  11. Qing K. Wang
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  12. Mugen Liu
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Correspondence to Qing K. Wang or Mugen Liu.

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Liu, P., Zhang, S., Yao, Q. et al. Identification of a genetic locus for autosomal dominant disseminated superficial actinic porokeratosis on chromosome 1p31.3–p31.1. Hum Genet 123, 507–513 (2008). https://doi.org/10.1007/s00439-008-0504-x

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  • DOI: https://doi.org/10.1007/s00439-008-0504-x

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