Table 1.
Mutations in TITF1/NKX2.1 with neurological, thyroid, lung, or pituitary involvement
| Mutation | Transmission | Brain | Thyroid | Lung | Brain MRI | N. patients with brain MRI | N. patients with pituitary abnormalities | Notes | References |
|---|---|---|---|---|---|---|---|---|---|
| §p.M59AfsX40 | De novo | + | – | + | NR | McMichael, 2013 [40] | |||
| §p.Y98X | De novo | + | + | – | NR | Tübing, 2018 [41] | |||
| p.Y98X | AD | + | + | + | – | 2 | Nakamura, 2012 [42] | ||
| p.Q107X | AD | + | – | – | – | 4 | Sempere, 2013 [43] | ||
| p.G115AfsX10 | De novo | + | – | + | – | 1 | Parnes, 2018 [28] | ||
| p.Y116fsX323 | De novo | + | + | + | – | 1 | Pohlenz, 2002 [44] | ||
| p.Y116X | AD | + | – | – | NR | Gras, 2012 [45] | |||
| p.C117X | ? | + | + | + | NR | Krude, 2002 [7] | |||
| p.P129fsX307 | De novo | + | – | + | NR | Hamvas, 2013 [46] | |||
| p.Y130X | De novo | + | + | + | – | 1 | Parnes, 2018 [28] | ||
| p.Y130X | De novo | + | + | + | – | 1 | Iodice, 2019 [47] | ||
| p.T133NfsX306 | De novo | – | + | + | – | 1 | Parnes, 2018 [28] | ||
| §p.W143X | De novo | + | + | – | + | 2 | 2 | Empty sella | Balicza, 2018 [10] |
| p.Y144X | ? | + | + | – | NR | Teissier, 2012 [48] | |||
| p.Y144X | ? | + | + | + | NR | Hamvas, 2013 [46] | |||
| §p.R157AfsX7 | De novo | + | + | – | – | 1 | Milone, 2019 [] | ||
| c.463 + 1_463 + 4del | AD | + | + | – | NR | Gras, 2012 [45] | |||
| c.463 + 1G > A | De novo | + | + | + | – | 1 | Fons, 2012 [49] | ||
| c.464-9C > A | AD | + | + | – | – | 6 | Konishi, 2013 [50] | ||
| c.464-1G > A | De novo | + | + | + | – | 1 | Barreiro, 2011 [51] | ||
| c.464-2A > C | AD | + | – | – | – | 2 | Asmus, 2007 [25] | ||
| c.464-2A > T | AD | + | – | NR | – | 1 | Kleiner-Fisman,2003 [31] | ||
| c.464-2A > G | AD | + | + | + | – | 2 | Doyle, 2004 [52] | ||
| c.464-2A > G | De novo | + | + | + | – | 1 | Carrè, 2009 [24] | ||
| p.S163fsX2 | De novo | + | + | + | NR | Gras, 2012 [45] | |||
| p.S175X | AD | + | + | + | + | 2 | 2 | Empty sella | Ferrara, 2008 [53]; Salvatore, 2010 [5] |
| p.P185fsX250 | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| p.P187fsX196 | De novo | + | + | + | – | 1 | Nagasaki, 2008 [54] | ||
| p.R195fsX32 | AD | + | + | + | _ | 1 | Nettore, 2013 [55] | ||
| p.R195W | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| p.L197P | ? | + | – | + | NR | Hamvas, 2013 [46] | |||
| p.F198L | AD | – | – | + | NR | Hamvas, 2013 [46] | |||
| p.F198L | ? | – | – | + | NR | Hamvas, 2013 [46] | |||
| p.F198L | ? | – | – | + | NR | Hamvas, 2013 [46] | |||
| p.S199X | ? | + | + | – | NR | Krude, 2002 [7] | |||
| §p.Q202H | De novo | + | + | – | – | Provenzano, 2016 [30] | |||
| p.Q202R | De novo | + | – | – | + | 1 | 1 | Empty sella | Present paper |
| p.E205X | AD | _ | – | – | – | 3 | Asmus, 2005 [56] | ||
| p.L206V | De novo | + | – | – | – | 1 | Gras, 2012 [45]; Carrè, 2009 [24] | ||
| p.R208X | AD | + | – | – | – | 1 | Provenzano, 2008 [57] | ||
| p.R209P | De novo | + | + | – | _ | 2 | Williamson, 2014 [58] | ||
| p.K211X | De novo | + | + | – | + | 2 | 2 | Cystic mass, empty sella | Veneziano, 2014 [8] |
| p.Y215D | De novo | + | + | – | NR | Gras, 2012 [45] | |||
| p.S217X | AD | + | + | – | NR | Glik, 2008 [20] | |||
| p.L224R | AD | + | + | – | NR | Gras, 2012 [45] | |||
| p.L224R | De novo | + | + | + | NR | Koht, 2016 [59] | |||
| p.A225fsX228 | De novo | + | – | – | NR | Krude, 2002 [7] | |||
| p.L230P | De novo | + | + | – | – | 1 | Iodice, 2019 [47] | ||
| p.P233L | De novo | + | + | – | NR | Carrè, 2009 [24] | |||
| p.V235P | De novo | + | + | + | + | 1 | 1 | Cystic mass | Krude, 2002 [7] |
| p.V235P | AD | + | + | – | – | 2 | Uematsu, 2012 [18] | ||
| p.I237F | De novo | NR | + | + | NR | Maquet, 2009 [60] | |||
| p.I237M | De novo | – | + | + | NR | Gillet, 2013 [61] | |||
| p.W238L | AD | + | NR | NR | – | 1 | Breedveld, 2002 [1] | ||
| p.W238CfsX9 | De novo | + | + | – | – | 1 | Iodice, 2019 [47] | ||
| §p.W238S | De novo | + | + | – | – | Provenzano, 2016 [30] | |||
| p.Q240P | De novo | + | + | – | – | 1 | Gras, 2012 [45]; Carrè, 2009 [24] | ||
| p.R243S | AD | + | NR | NR | – | 1 | Breedveld, 2002 [1] | ||
| p.R243P | AD | + | – | – | NR | Gras, 2012 [45] | |||
| p.Y244X | AD | + | + | – | NR | Gras, 2012 [45] | |||
| p.Q249X | AD | + | – | – | – | 2 | Costa, 2005 [62] | ||
| p.D252VfsX187 | De novo | + | + | + | – | 1 | Parnes, 2018 [28] | ||
| p.G266del | AD | + | NR | + | – | 1 | Zorzi, 2008 [63] | ||
| p.G269_271dupGGGa | ? | + | – | + | NR | Hamvas, 2013 [46] | |||
| p.274_280del7aa and p.G273fsX152 | ? | + | + | + | NR | Hamvas, 2013 [46] | |||
| p.A280fsX161 | AD | + | + | + | NR | Teissier, 2012 [48] | |||
| p.P291R | De novo | + | + | – | – | 1 | Iodice, 2019 [47] | ||
| p.L293del | De novo | + | + | + | NR | Gras, 2012 [45] | |||
| p.G303fsX77 | AD | + | NR | NR | – | 1 | Breedveld, 2002 [1] | ||
| p.A306fsX350 | AD | + | + | – | – | 2 | Moya, 2006 [37] | ||
| p.Q327fsX121 | De novo | + | + | + | – | 1 | Willemsen, 2005 [4] | ||
| p.A327GfsX52 | De novo | + | + | + | NR | Shetty, 2014 [64] | |||
| p.A329GfsX108 | De novo | + | + | + | NR | Hermanns, 2018 [65] | |||
| p.A333RfsX132 | De novo | + | + | + | – | 1 | Tozawa, 2016 [66] | ||
| p.H349fsX90 | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| p.Q357fsX24 | AD | + | – | – | – | 3 | Mahajnah, 2007 [39] | ||
| p.S366fsX67 | ? | – | + | + | NR | Hamvas, 2013 [46] | |||
| p.T389fsX52 | ? | + | + | + | NR | Hamvas, 2013 [46] | |||
| del 14q13-q21 | De novo | NR | + | + | – | 1 | Devriendt , 1998 [67] | ||
| del 14q12-q13.3 | De novo | + | + | + | –b | 2 | Iwatani, 2000 [68] | ||
| del 14 1.2 MB | De novo | + | NR | NR | – | 1 | Breedveld, 2002 [1] | ||
| del 14 1.2 MB | AD | + | + | NR | + | 2 | 1 | Stalk duplication | Accornero, 2010 [35] |
| del 14q11.2-q13.3 | ? | + | + | + | + | 1 | 1 | Cystic mass | Krude, 2002 [7] |
| del 14q13 | De novo | + | + | + | – | 1 | Carrè, 2009 [24] | ||
| del 14 0.9 MB | AD | + | + | + | – | 3 | Devos, 2006 [69] | ||
| del 14q12-q13 | De novo | + | + | + | – | 1 | Uematsu, 2012 [18] | ||
| del 14q13.2-q22.1 | De novo | + | – | – | NR | Gras, 2012 [45] | |||
| del 14q13.2-q21.2 | De novo | + | + | – | NR | Gras, 2012 [45] | |||
| del 14q13.3 | De novo | + | + | – | NR | Gras, 2012 [45] | |||
| del 14q13.1-q21.1 | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| del 14q13.3 | ? | + | + | + | NR | Hamvas, 2013 [46] | |||
| del 14q13.3-q21.1 | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| del 14q13.1-q21.1 | De novo | + | + | + | NR | Hamvas, 2013 [46] | |||
| DEL ex1-2 | ? | + | + | + | NR | Hamvas, 2013 [46] | |||
| del 14q13.2-q21.1 | De novo | + | + | – | – | 1 | Dale, 2012 [70] | ||
| del 14q13.3 | AD | + | + | + | NR | Teissier, 2012 [48] | |||
| del 14q13.3 | De novo | + | + | – | NR | Teissier, 2012 [48] | |||
| del 14q13.2-q21.1 | De novo | + | + | + | – | 1 | Villafuerte, 2018 [71] |
AD autosomal dominant, NR not recorded, ? unknown, § these mutations, published according to the short NKX2.1 isoform, have been reported to the long isoform ref seq NM_001079668.3, NP_001073136.1.