TY - JOUR
T1 - Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of kitamura, a clinical entity distinct from dowling-degos disease
AU - Kono, Michihiro
AU - Sugiura, Kazumitsu
AU - Suganuma, Mutsumi
AU - Hayashi, Masahiro
AU - Takama, Hiromichi
AU - Suzuki, Tamio
AU - Matsunaga, UKayoko
AU - Tomita, Yasushi
AU - Akiyama, Masashi
N1 - Funding Information:
A grant from the Ministry of Health, Labor and Welfare of Japan (Health and Labor Sciences Research Grants, Research on Measures for Intractable Diseases, H23-070) (to M.K.) and Grants-in-Aid for Scientific Research (A) 23249058 (to M.A.) and (C) 24591646 (to M.K.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT).
PY - 2013/9
Y1 - 2013/9
N2 - Reticulate acropigmentation of Kitamura (RAK) is a rare genetic disorder of cutaneous pigmentation with an autosomal dominant pattern of inheritanceanda high penetration rate.Thecharacteristic skin lesions are reticulate, slightly depressed pigmented macules mainly affecting the dorsa of the hands and feet, which first appear before puberty and subsequently expand to the proximal limb and the trunk. To identify mutations that cause RAK, we performed exome sequencing of four family members in a pedigree with RAK. Fifty-three SNV/Indels were considered as candidate mutations after some condition narrowing. We confirmed the mutation status in each candidate gene of four othermembers in the same pedigree to find the gene that matched the mutation status and pheno type of each member. Amutation in ADAM10 encodingazinc metalloprotease, adisintegrinand metalloprotease domain-containing protein 10 (ADAM10), was identified in theRAKfamily. ADAM10 is known to be involved in the ectodomain shedding of various substrates in the skin. Sanger sequencing of four additional unrelated RAK patients revealed four additional ADAM10 mutations. We identified a total of three truncating mutations, a splice site mutation and a missense mutation in ADAM10. We searched for mutations in the KRT5 gene, a causative gene for the similar pigmentation disorder Dowling-Degos disease (DDD), in all the patients and found no KRT5 mutation. These results reveal that mutations in ADAM10 are a cause of RAK and that RAK is an independent clinical entity distinct from DDD.
AB - Reticulate acropigmentation of Kitamura (RAK) is a rare genetic disorder of cutaneous pigmentation with an autosomal dominant pattern of inheritanceanda high penetration rate.Thecharacteristic skin lesions are reticulate, slightly depressed pigmented macules mainly affecting the dorsa of the hands and feet, which first appear before puberty and subsequently expand to the proximal limb and the trunk. To identify mutations that cause RAK, we performed exome sequencing of four family members in a pedigree with RAK. Fifty-three SNV/Indels were considered as candidate mutations after some condition narrowing. We confirmed the mutation status in each candidate gene of four othermembers in the same pedigree to find the gene that matched the mutation status and pheno type of each member. Amutation in ADAM10 encodingazinc metalloprotease, adisintegrinand metalloprotease domain-containing protein 10 (ADAM10), was identified in theRAKfamily. ADAM10 is known to be involved in the ectodomain shedding of various substrates in the skin. Sanger sequencing of four additional unrelated RAK patients revealed four additional ADAM10 mutations. We identified a total of three truncating mutations, a splice site mutation and a missense mutation in ADAM10. We searched for mutations in the KRT5 gene, a causative gene for the similar pigmentation disorder Dowling-Degos disease (DDD), in all the patients and found no KRT5 mutation. These results reveal that mutations in ADAM10 are a cause of RAK and that RAK is an independent clinical entity distinct from DDD.
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U2 - 10.1093/hmg/ddt207
DO - 10.1093/hmg/ddt207
M3 - Article
C2 - 23666529
AN - SCOPUS:84881603740
SN - 0964-6906
VL - 22
SP - 3524
EP - 3533
JO - Human molecular genetics
JF - Human molecular genetics
IS - 17
M1 - ddt207
ER -