Abstract
Background: Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. Objective: We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). Methods: Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. Results: From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (. SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. Conclusion: We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.
| Original language | English |
|---|---|
| Pages (from-to) | 36-44 |
| Number of pages | 9 |
| Journal | Journal of Dermatological Science |
| Volume | 68 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2012 Oct |
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Keywords
- CVG
- Mutation analysis
- NGS
- PDP
- PGT
- Prostaglandin transporter
- SLCO2A1
- SNP
- Whole exome sequencing
ASJC Scopus subject areas
- Dermatology
- Biochemistry
- Molecular Biology
Cite this
Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype-genotype correlation in Japanese patients with pachydermoperiostosis. / Sasaki, Takashi; Niizeki, Hironori; Shimizu, Atsushi; Shiohama, Aiko; Hirakiyama, Asami; Okuyama, Torayuki; Seki, Atsuhito; Kabashima, Kenji; Otsuka, Atsushi; Ishiko, Akira; Tanese, Keiji; Miyakawa, Shun Ichi; Sakabe, Jun Ichi; Kuwahara, Masamitsu; Amagai, Masayuki; Okano, Hideyuki; Suematsu, Makoto; Kudo, Jun.
In: Journal of Dermatological Science, Vol. 68, No. 1, 10.2012, p. 36-44.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of mutations in the prostaglandin transporter gene SLCO2A1 and its phenotype-genotype correlation in Japanese patients with pachydermoperiostosis
AU - Sasaki, Takashi
AU - Niizeki, Hironori
AU - Shimizu, Atsushi
AU - Shiohama, Aiko
AU - Hirakiyama, Asami
AU - Okuyama, Torayuki
AU - Seki, Atsuhito
AU - Kabashima, Kenji
AU - Otsuka, Atsushi
AU - Ishiko, Akira
AU - Tanese, Keiji
AU - Miyakawa, Shun Ichi
AU - Sakabe, Jun Ichi
AU - Kuwahara, Masamitsu
AU - Amagai, Masayuki
AU - Okano, Hideyuki
AU - Suematsu, Makoto
AU - Kudo, Jun
PY - 2012/10
Y1 - 2012/10
N2 - Background: Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. Objective: We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). Methods: Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. Results: From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (. SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. Conclusion: We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.
AB - Background: Pachydermoperiostosis (PDP) is a rare genetic disorder characterized by 3 major symptoms: pachydermia including cutis verticis gyrata (CVG), periostosis, and finger clubbing. Recently, a homozygous mutation in the gene HPGD, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), was found to be associated with PDP. However, mutations in HPGD have not been identified in Japanese PDP patients. Objective: We aimed to identify a novel responsible gene for PDP using whole exome sequencing by next-generation DNA sequencer (NGS). Methods: Five patients, including 2 patient-parent trios were enrolled in this study. Entire coding regions were sequenced by NGS to identify candidate mutations associated with PDP. The candidate mutations were subsequently sequenced using the Sanger method. To determine clinical characteristics, we analyzed histological samples, as well as serum and urinary prostaglandin E2 (PGE2) levels for each of the 5 PDP patients, and 1 additional patient with idiopathic CVG. Results: From initial analyses of whole exome sequencing data, we identified mutations in the solute carrier organic anion transporter family, member 2A1 (. SLCO2A1) gene, encoding prostaglandin transporter, in 3 of the PDP patients. Follow-up Sanger sequencing showed 5 different SLCO2A1 mutations (c.940+1G>A, p.E427_P430del, p.G104*, p.T347I, p.Q556H) in 4 unrelated PDP patients. In addition, the splice-site mutation c.940+1G>A identified in 3 of 4 PDP patients was determined to be a founder mutation in the Japanese population. Furthermore, it is likely that the combination of these SLCO2A1 mutations in PDP patients is also associated with disease severity. Conclusion: We found that SLCO2A1 is a novel gene responsible for PDP. Although the SLCO2A1 gene is only the second gene discovered to be associated with PDP, it is likely to be a major cause of PDP in the Japanese population.
KW - CVG
KW - Mutation analysis
KW - NGS
KW - PDP
KW - PGT
KW - Prostaglandin transporter
KW - SLCO2A1
KW - SNP
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=84865771808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865771808&partnerID=8YFLogxK
U2 - 10.1016/j.jdermsci.2012.07.008
DO - 10.1016/j.jdermsci.2012.07.008
M3 - Article
VL - 68
SP - 36
EP - 44
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 1
ER -