Functionally confirmed compound heterozygous ADAM17 missense loss-of-function variants cause neonatal inflammatory skin and bowel disease 1.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
05 05 2021
Historique:
received: 04 02 2021
accepted: 13 04 2021
entrez: 6 5 2021
pubmed: 7 5 2021
medline: 28 10 2021
Statut: epublish

Résumé

A disintegrin and metalloprotease 17 (ADAM17) is the major sheddase that processes more than 80 substrates, including tumour necrosis factor-α (TNFα). The homozygous genetic deficiency of ADAM17 causing a complete loss of ADAM17 expression was reported to be linked to neonatal inflammatory skin and bowel disease 1 (NISBD1). Here we report for the first time, a family with NISBD1 caused by functionally confirmed compound heterozygous missense variants of ADAM17, namely c.1699T>C (p.Cys567Arg) and c.1799G>A (p.Cys600Tyr). Both variants were detected in two siblings with clinical features of NISBD1, such as erythroderma with exudate in whole body, recurrent skin infection and sepsis and prolonged diarrhoea. In a cell-based assay using Adam10/17 double-knockout mouse embryonic fibroblasts (Adam10/17

Identifiants

pubmed: 33953303
doi: 10.1038/s41598-021-89063-0
pii: 10.1038/s41598-021-89063-0
pmc: PMC8100128
doi:

Substances chimiques

ADAM17 Protein EC 3.4.24.86
ADAM17 protein, human EC 3.4.24.86

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9552

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Auteurs

Issei Imoto (I)

Risk Assessment Center, Aichi Cancer Center Hospital, Nagoya, Japan. iimoto@aichi-cc.jp.
Division of Molecular Genetics, Aichi Cancer Center Research Institute, Nagoya, Japan. iimoto@aichi-cc.jp.
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan. iimoto@aichi-cc.jp.

Masako Saito (M)

Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Kenichi Suga (K)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Tomohiro Kohmoto (T)

Division of Molecular Genetics, Aichi Cancer Center Research Institute, Nagoya, Japan.
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Masanobu Otsu (M)

Department of Dermatology, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Keisuke Horiuchi (K)

National Defense Medical Collage, Saitama, Japan.

Hironao Nakayama (H)

Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, 791-0925, Japan.

Shigeki Higashiyama (S)

Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Ehime, 791-0925, Japan.

Mayumi Sugimoto (M)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Ayumi Sasaki (A)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Yukako Homma (Y)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Miki Shono (M)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Ryuji Nakagawa (R)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Yasunobu Hayabuchi (Y)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Shoichiro Tange (S)

Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Shoji Kagami (S)

Department of Pediatrics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.

Kiyoshi Masuda (K)

Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Kawasaki Medical School, Kurashiki, 701-0192, Japan.

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Classifications MeSH