Highly prevalent SERPINB7 founder mutation causes pseudodominant inheritance pattern in Nagashima-type palmoplantar keratosis.
BACKGROUND
Nagashima-type palmoplantar keratosis (NPPK) is a distinct autosomal recessive genodermatosis characterized by diffuse transgressive palmoplantar keratoderma (PPK). Very recently, putative loss-of-function mutations in SERPINB7, which encodes a member of the serine protease inhibitor superfamily and is abundantly expressed in the epidermis, have been identified as a cause of NPPK.


OBJECTIVE
To confirm further the role of SERPINB7 mutations in the pathogenesis of NPPK.


METHODS
We analysed 10 Japanese families with NPPK using Sanger and/or whole-exome sequencing.


RESULTS
We identified one novel and three recurrent null mutations in SERPINB7. In all the families, the NPPK trait was inherited in an autosomal recessive manner; in one of the families, there was pseudodominant inheritance, which had not been described in NPPK.


CONCLUSIONS
These data clearly provide further evidence that NPPK is caused by loss-of-function mutations in SERPINB7.
Department of Dermatology, Hokkaido University Graduate School of Medicine, North 15 West 7, Kita-ku, 060-8638, Sapporo, Japan.
O
O
Mizuno
T
T
Nomura
S
S
Suzuki
M
M
Takeda
Y
Y
Ohguchi
Y
Y
Fujita
W
W
Nishie
K
K
Sugiura
M
M
Akiyama
H
H
Shimizu
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D018703:Founder Effect; D005799:Genes, Dominant / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D040582:Inheritance Patterns; D007645:Keratoderma, Palmoplantar / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D015843:Serpins / Q000235:genetics*
C114170:SERPINB7 protein, human; D015843:Serpins