Details

Autor(en) / Beteiligte

• Takagi, Masatoshi, MD, PhD
• Ogata, Shohei, MD, PhD
• Ueno, Hiroo, MD
• Yoshida, Kenichi, MD, PhD
• Yeh, Tzuwen, BSc
• Hoshino, Akihiro, MD, PhD
• Piao, Jinhua, DDS, PhD
• Yamashita, Motoy, MD
• Nanya, Mai, PhD
• Okano, Tsubasa, MD
• Kajiwara, Michiko, MD, PhD
• Kanegane, Hirokazu, MD, PhD
• Muramatsu, Hideki, MD, PhD
• Okuno, Yusuke, MD, PhD
• Shiraishi, Yuichi, MD, PhD
• Chiba, Kenichi, BA
• Tanaka, Hiroko, BS
• Bando, Yuki, MD, PhD
• Kato, Motohiro, MD, PhD
• Hayashi, Yasuhide, MD, PhD
• Miyano, Satoru, PhD
• Imai, Kohsuke, MD, PhD
• Ogawa, Seishi, MD, PhD
• Kojima, Seiji, MD, PhD
• Morio, Tomohiro, MD, PhD

Titel

Haploinsufficiency of TNFAIP3 ( A20 ) by germline mutation is involved in autoimmune lymphoproliferative syndrome

Ist Teil von

• Journal of allergy and clinical immunology, 2017-06, Vol.139 (6), p.1914-1922

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background Autoimmune diseases in children are rare and can be difficult to diagnose. Autoimmune lymphoproliferative syndrome (ALPS) is a well-characterized pediatric autoimmune disease caused by mutations in genes associated with the FAS-dependent apoptosis pathway. In addition, various genetic alterations are associated with the ALPS-like phenotype. Objective The aim of the present study was to elucidate the genetic cause of the ALPS-like phenotype. Methods Candidate genes associated with the ALPS-like phenotype were screened by using whole-exome sequencing. The functional effect of the identified mutations was examined by analyzing the activity of related signaling pathways. Results A de novo heterozygous frameshift mutation of TNF-α–induced protein 3 (TNFAIP3, A20), a negative regulator of the nuclear factor κB pathway, was identified in one of the patients exhibiting the ALPS-like phenotype. Increased activity of the nuclear factor κB pathway was associated with haploinsufficiency of TNFAIP3 (A20). Conclusion Haploinsufficiency of TNFAIP3 (A20) by a germline heterozygous mutation leads to the ALPS phenotype.