A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome.
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.
1Department of Paediatrics, NHS Ayrshire and Arran, Crosshouse Hospital, Kilmarnock, United Kingdom.
Scott
S
Williamson
Martin
M
Kirkpatrick
Stephen
S
Greene
David
D
Goudie
D001264:Athetosis / Q000235:genetics*; D002819:Chorea / Q000235:genetics*; D003409:Congenital Hypothyroidism / Q000235:genetics*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D012127:Respiratory Distress Syndrome, Newborn / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors
NKX2-1; TTF-1; benign hereditary chorea; brain-thyroid-lung syndrome; hypothyroidism