OBJECTIVE: Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG gene (locus: Xq22.2), which result in defective synthesis or changes in the physical properties or biological function of a protein. DESIGN: We report a novel mutation of the TBG gene causing a complete TBG deficiency in three brothers of Polish origin. DNA was extracted from all of the family members and subjected to sequence analysis. We analyzed the family with a heterozygous mother, a normal father, their three hemizygous affected sons, and their two normal sons. MAIN OUTCOME: Our studies revealed a novel mutation, a single nucleotide deletion (guanine) at position 1711, codon 201 (Asp) in exon 2 (GAC --> AC). This mutation led to a frame shift and premature termination at codon 206, causing a short TBG protein of 205 amino acids (AA) compared to 395 AA of the normal TBG. This new TBG-CD variant was found in the mother and her three affected sons. CONCLUSION: This is a new variant of TBG-CD (TBG-CD-PL Poland) containing 205 AA.
OBJECTIVE: Inherited thyroxine-binding globulin (TBG) deficiency is caused by mutations in the TBG gene (locus: Xq22.2), which result in defective synthesis or changes in the physical properties or biological function of a protein. DESIGN: We report a novel mutation of the TBG gene causing a complete TBG deficiency in three brothers of Polish origin. DNA was extracted from all of the family members and subjected to sequence analysis. We analyzed the family with a heterozygous mother, a normal father, their three hemizygous affected sons, and their two normal sons. MAIN OUTCOME: Our studies revealed a novel mutation, a single nucleotide deletion (guanine) at position 1711, codon 201 (Asp) in exon 2 (GAC --> AC). This mutation led to a frame shift and premature termination at codon 206, causing a short TBG protein of 205 amino acids (AA) compared to 395 AA of the normal TBG. This new TBG-CD variant was found in the mother and her three affected sons. CONCLUSION: This is a new variant of TBG-CD (TBG-CD-PL Poland) containing 205 AA.
Authors: Ganna Chornokur; Hui-Yi Lin; Jonathan P Tyrer; Kate Lawrenson; Joe Dennis; Ernest K Amankwah; Xiaotao Qu; Ya-Yu Tsai; Heather S L Jim; Zhihua Chen; Ann Y Chen; Jennifer Permuth-Wey; Katja K H Aben; Hoda Anton-Culver; Natalia Antonenkova; Fiona Bruinsma; Elisa V Bandera; Yukie T Bean; Matthias W Beckmann; Maria Bisogna; Line Bjorge; Natalia Bogdanova; Louise A Brinton; Angela Brooks-Wilson; Clareann H Bunker; Ralf Butzow; Ian G Campbell; Karen Carty; Jenny Chang-Claude; Linda S Cook; Daniel W Cramer; Julie M Cunningham; Cezary Cybulski; Agnieszka Dansonka-Mieszkowska; Andreas du Bois; Evelyn Despierre; Ed Dicks; Jennifer A Doherty; Thilo Dörk; Matthias Dürst; Douglas F Easton; Diana M Eccles; Robert P Edwards; Arif B Ekici; Peter A Fasching; Brooke L Fridley; Yu-Tang Gao; Aleksandra Gentry-Maharaj; Graham G Giles; Rosalind Glasspool; Marc T Goodman; Jacek Gronwald; Patricia Harrington; Philipp Harter; Alexander Hein; Florian Heitz; Michelle A T Hildebrandt; Peter Hillemanns; Claus K Hogdall; Estrid Hogdall; Satoyo Hosono; Anna Jakubowska; Allan Jensen; Bu-Tian Ji; Beth Y Karlan; Linda E Kelemen; Mellissa Kellar; Lambertus A Kiemeney; Camilla Krakstad; Susanne K Kjaer; Jolanta Kupryjanczyk; Diether Lambrechts; Sandrina Lambrechts; Nhu D Le; Alice W Lee; Shashi Lele; Arto Leminen; Jenny Lester; Douglas A Levine; Dong Liang; Boon Kiong Lim; Jolanta Lissowska; Karen Lu; Jan Lubinski; Lene Lundvall; Leon F A G Massuger; Keitaro Matsuo; Valerie McGuire; John R McLaughlin; Iain McNeish; Usha Menon; Roger L Milne; Francesmary Modugno; Kirsten B Moysich; Roberta B Ness; Heli Nevanlinna; Ursula Eilber; Kunle Odunsi; Sara H Olson; Irene Orlow; Sandra Orsulic; Rachel Palmieri Weber; James Paul; Celeste L Pearce; Tanja Pejovic; Liisa M Pelttari; Malcolm C Pike; Elizabeth M Poole; Harvey A Risch; Barry Rosen; Mary Anne Rossing; Joseph H Rothstein; Anja Rudolph; Ingo B Runnebaum; Iwona K Rzepecka; Helga B Salvesen; Eva Schernhammer; Ira Schwaab; Xiao-Ou Shu; Yurii B Shvetsov; Nadeem Siddiqui; Weiva Sieh; Honglin Song; Melissa C Southey; Beata Spiewankiewicz; Lara Sucheston; Soo-Hwang Teo; Kathryn L Terry; Pamela J Thompson; Lotte Thomsen; Ingvild L Tangen; Shelley S Tworoger; Anne M van Altena; Robert A Vierkant; Ignace Vergote; Christine S Walsh; Shan Wang-Gohrke; Nicolas Wentzensen; Alice S Whittemore; Kristine G Wicklund; Lynne R Wilkens; Anna H Wu; Xifeng Wu; Yin-Ling Woo; Hannah Yang; Wei Zheng; Argyrios Ziogas; Hanis N Hasmad; Andrew Berchuck; Edwin S Iversen; Joellen M Schildkraut; Susan J Ramus; Ellen L Goode; Alvaro N A Monteiro; Simon A Gayther; Steven A Narod; Paul D P Pharoah; Thomas A Sellers; Catherine M Phelan Journal: PLoS One Date: 2015-06-19 Impact factor: 3.240