TY - JOUR
T1 - A Novel Mutation in NKX2-1 Shows Dominant-Negative Effects only in the Presence of PAX8
AU - Shinohara, Hiroyuki
AU - Takagi, Masaki
AU - Ito, Kimiko
AU - Shimizu, Eri
AU - Fukuzawa, Ryuji
AU - Hasegawa, Tomonobu
N1 - Funding Information:
The authors thank Dr. S. Narumi (Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan) for the TG-Luc reporter construct. This work was supported by a Grant from the Japan Society for the Promotion of Science (16K10007), Takeda Science Foundation, and the Foundation for Growth Science, Japan.
Publisher Copyright:
© Copyright 2018, Mary Ann Liebert, Inc. 2018.
PY - 2018/8
Y1 - 2018/8
N2 - To date, >100 mutations in NKX2-1 have been described. Most NKX2-1 mutations are assumed to result in brain-lung-thyroid syndrome through haploinsufficiency, and only five NKX2-1 mutations with dominant-negative effects have been reported so far. In this case report, an additional patient with brain-lung-thyroid syndrome is reported, carrying a novel heterozygous mutation, c.533G>C (p.R178P), in the homeobox of NKX2-1. This mutation has been proven to be a dominant-negative mutation by an in vitro functional assay. Of note, the dominant-negative effect of R178P-NKX2-1 was shown only in the presence of PAX8.
AB - To date, >100 mutations in NKX2-1 have been described. Most NKX2-1 mutations are assumed to result in brain-lung-thyroid syndrome through haploinsufficiency, and only five NKX2-1 mutations with dominant-negative effects have been reported so far. In this case report, an additional patient with brain-lung-thyroid syndrome is reported, carrying a novel heterozygous mutation, c.533G>C (p.R178P), in the homeobox of NKX2-1. This mutation has been proven to be a dominant-negative mutation by an in vitro functional assay. Of note, the dominant-negative effect of R178P-NKX2-1 was shown only in the presence of PAX8.
KW - NKX2-1
KW - PAX8
KW - brain-lung-thyroid syndrome
KW - dominant-negative effect
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U2 - 10.1089/thy.2017.0481
DO - 10.1089/thy.2017.0481
M3 - Article
C2 - 29882472
AN - SCOPUS:85051530282
SN - 1050-7256
VL - 28
SP - 1071
EP - 1073
JO - Thyroid
JF - Thyroid
IS - 8
ER -
