title: Exome sequencing identifies SLC17A9 pathogenic gene in two Chinese pedigrees with disseminated superficial actinic porokeratosis.
abstract: BACKGROUND
  Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant genodermatosis characterised by annular lesions that has an atrophic centre and a prominent peripheral ridge distributed on sun exposed area. It exhibits high heterogeneity, and five linkage loci have been reported. The mevalonate kinase (MVK) gene located on 12q24 has been confirmed as one of the disease-causing genes. But, the pathogenesis of a large part of DSAP remains unclear so far.
  
  
  METHODS
  The recruited with DSAP carried no MVK coding mutations. Exome sequencing was performed in two affected and one unaffected individual in Family 1. Cosegregation of the candidate variants was tested in other family members. Sanger sequencing in 33 individuals with familial DSAP and 19 sporadic DSAP individuals was performed for validating the causative gene.
  
  
  RESULTS
  An average of 1.35×10(5) variants were generated from exome data and 133 novel NS/SS/indels were identified as being shared by two affected individuals but absent in the unaffected individual. After functional prediction, 25 possible deleterious variants were identified. In Family 1, a missense variant c.932G>A (p.Arg311Gln) in exon 10 of SLC17A9 was observed in cosegregation with the phenotype; this amino acid substitution was located in a highly conserved major facilitator superfamily (MFS) domain in multiple mammalian. One additional missense variant c.25C>T (p.Arg9Cys) in exon 2 of SLC17A9 was found in Family 2.
  
  
  CONCLUSIONS
  The result identified SLC17A9 as another pathogenic gene for DSAP, which suggests a correlation between the aberrant vesicular nucleotide transporter and the pathogenesis of DSAP.
authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China Department of Dermatology at No.2 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
authors.forename: Hongzhou
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authors.lastname: Cui
authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
authors.forename: Longnian
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.lastname: Wang
authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
authors.forename: Xiaodong
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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authors.affiliation: Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China Department of Dermatology at No.2 Hospital, Anhui Medical University, Hefei, Anhui, China Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui, China State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology & Key Laboratory of Dermatology, Ministry of Education & Key Laboratory of Dermatology, Hefei, Anhui, China.
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mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D059472:Exome; D005260:Female; D006801:Humans; D008297:Male; D033704:Nucleotide Transport Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017499:Porokeratosis / Q000235:genetics*
chemical_list: D033704:Nucleotide Transport Proteins; C529437:Slc17a9 protein, human
keywords: Cancer: Dermatological; Clinical Genetics; Dermatology; Genetic Screening/Counselling; Genetics