Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of kitamura, a clinical entity distinct from dowling-degos disease

Michihiro Kono, Kazumitsu Sugiura, Mutsumi Suganuma, Masahiro Hayashi, Hiromichi Takama, Tamio Suzuki, UKayoko Matsunaga, Yasushi Tomita, Masashi Akiyama

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article numberddt207
Pages (from-to)3524-3533
Number of pages10
JournalHuman molecular genetics
Volume22
Issue number17
DOIs
Publication statusPublished - 01-09-2013

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Exome
Mutation
Metalloproteases
Pedigree
Genes
Pigmentation Disorders
Dowling-Degos Disease
Skin Pigmentation
Skin
Inborn Genetic Diseases
Missense Mutation
Puberty
Foot
Extremities
Hand

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kono, Michihiro ; Sugiura, Kazumitsu ; Suganuma, Mutsumi ; Hayashi, Masahiro ; Takama, Hiromichi ; Suzuki, Tamio ; Matsunaga, UKayoko ; Tomita, Yasushi ; Akiyama, Masashi. / Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of kitamura, a clinical entity distinct from dowling-degos disease. In: Human molecular genetics. 2013 ; Vol. 22, No. 17. pp. 3524-3533.
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abstract = "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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Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of kitamura, a clinical entity distinct from dowling-degos disease. / Kono, Michihiro; Sugiura, Kazumitsu; Suganuma, Mutsumi; Hayashi, Masahiro; Takama, Hiromichi; Suzuki, Tamio; Matsunaga, UKayoko; Tomita, Yasushi; Akiyama, Masashi.

In: Human molecular genetics, Vol. 22, No. 17, ddt207, 01.09.2013, p. 3524-3533.

Research output: Contribution to journalArticle

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AU - Kono, Michihiro

AU - Sugiura, Kazumitsu

AU - Suganuma, Mutsumi

AU - Hayashi, Masahiro

AU - Takama, Hiromichi

AU - Suzuki, Tamio

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AU - Tomita, Yasushi

AU - Akiyama, Masashi

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