Fine mapping and identification of a candidate gene SSH1 in disseminated superficial actinic porokeratosis.
Disseminated superficial actinic porokeratosis (DSAP) is an uncommon autosomal dominant chronic keratinization disorder, characterized by multiple superficial keratotic lesions surrounded by a slightly raised keratotic border. Thus far, although two loci for DSAP have been identified, the genetic basis and pathogenesis of this disorder have not been elucidated yet. In this study, we performed a genome-wide linkage analysis in three Chinese affected families and localized the gene in an 8.0 cM interval defined by D12S330 and D12S354 on chromosome 12. Upon screening 30 candidate genes, we identified a missense mutation, p.Ser63Asn in SSH1 in one family, a frameshift mutation, p.Ser19CysfsX24 in an alternative variant (isoform f) of SSH1 in another family, and a frameshift mutation, p.Pro27ProfsX54 in the same alternative variant in one non-familial case with DSAP. SSH1 encodes a phosphatase that plays a pivotal role in actin dynamics. Our data suggested that cytoskeleton disorganization in epidermal cells is likely associated with the pathogenesis of DSAP.
Zhang
Zhenghua
Z
Chinese National Human Genome Center at Shanghai and Health Science Center, SIBS, CAS and SSMU, Shanghai, P.R.China.
Niu
Zhenmin
Z
Yuan
Wentao
W
Liu
Weida
W
Xiang
Leihong
L
Zhang
Jing
J
Chu
Xun
X
Zhao
Jingjun
J
Jiang
Faxing
F
Chai
Bao
B
Cui
Fan
F
Wang
Ying
Y
Zhang
Kaiyue
K
Wang
Yi
Y
Xu
Shijie
S
Xia
Longqing
L
Gu
Jun
J
Zhang
Shoumin
S
Meng
Xuemei
X
Wang
Shuxia
S
Gao
Shunqiang
S
Fan
Min
M
Nie
Lei
L
Zheng
Zhizhong
Z
Huang
Wei
W
D017668:Age of Onset; D000368:Aged; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D017499:Porokeratosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*
D010749:Phosphoprotein Phosphatases; C484329:SSH1 protein, human