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.
Chinese National Human Genome Center at Shanghai and Health Science Center, SIBS, CAS and SSMU, Shanghai, P.R.China.
Zhenghua
Z
Zhang
Zhenmin
Z
Niu
Wentao
W
Yuan
Weida
W
Liu
Leihong
L
Xiang
Jing
J
Zhang
Xun
X
Chu
Jingjun
J
Zhao
Faxing
F
Jiang
Bao
B
Chai
Fan
F
Cui
Ying
Y
Wang
Kaiyue
K
Zhang
Yi
Y
Wang
Shijie
S
Xu
Longqing
L
Xia
Jun
J
Gu
Shoumin
S
Zhang
Xuemei
X
Meng
Shuxia
S
Wang
Shunqiang
S
Gao
Min
M
Fan
Lei
L
Nie
Zhizhong
Z
Zheng
Wei
W
Huang
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