TY - JOUR
T1 - A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis
T2 - part of the spectrum of brain-thyroid-lung syndrome
AU - Williamson, Scott
AU - Kirkpatrick, Martin
AU - Greene, Stephen
AU - Goudie, David
PY - 2014/5
Y1 - 2014/5
N2 - The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid transcription factor 1 (TTF-1). It is expressed in the developing brain, lung, and thyroid. Defects have been associated with chorea, hypothyroidism, and lung disease, comprising the "brain-thyroid-lung syndrome." We describe here 3 cases of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset hypothyroidism and a movement disorder characterized by ataxia in the early years followed by the emergence of a superimposed chorea. The mutation was also found in the granddaughter, when she presented with the same clinical features. We hypothesize that the mutation arose as a result of gonadal mosaicism, as the mutation was not detected in leucocyte DNA from either grandparent. The features are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously could have been classified as benign hereditary chorea with hypothyroidism.
AB - The NKX2-1 (TTF-1 or TITF-1) gene on chromosome 14q13 codes for the thyroid transcription factor 1 (TTF-1). It is expressed in the developing brain, lung, and thyroid. Defects have been associated with chorea, hypothyroidism, and lung disease, comprising the "brain-thyroid-lung syndrome." We describe here 3 cases of novel missense mutation (c.626G>C; p.Arg209Pro) in NKX2-1 in 2 generations of a nonconsanguinous family. Firstly 2 sons were affected by childhood-onset hypothyroidism and a movement disorder characterized by ataxia in the early years followed by the emergence of a superimposed chorea. The mutation was also found in the granddaughter, when she presented with the same clinical features. We hypothesize that the mutation arose as a result of gonadal mosaicism, as the mutation was not detected in leucocyte DNA from either grandparent. The features are consistent with a diagnosis of Brain-thyroid-lung syndrome, which previously could have been classified as benign hereditary chorea with hypothyroidism.
UR - http://www.scopus.com/inward/record.url?scp=84899703220&partnerID=8YFLogxK
U2 - 10.1177/0883073813518243
DO - 10.1177/0883073813518243
M3 - Article
C2 - 24453141
AN - SCOPUS:84899703220
SN - 0883-0738
VL - 29
SP - 666
EP - 669
JO - Journal of Child Neurology
JF - Journal of Child Neurology
IS - 5
ER -