Targovnik_2010_Clin.Endocrinol.(Oxf)_72_716

The index patient II-1 was the first child born from healthy and unrelated parents. She was born at term (gestational age: 39 weeks) with a body weight of 3050 g, a body height of 49.5 cm and a cranial circumference of 34.5 cm. At the age of 8 days, neonatal screening was positive for TSH (243 uIU/ml; reference values: 0.5-5), and thus the newborn was referred to a paediatric endocrinologist. Clinical examination was normal. Hormonal tests confirmed the diagnosis of hypothyroidism: TSH 533 uIU/ml, Free T4: 2.32 pmol/l (reference values: 10.3-23.2 pmol/l), Free T3: 2.2 pmol/l (reference values: 2.6-5.4 pmol/l). Searches for antithyroid peroxydase and antiTG antibodies were negatives. Serum TG was undetectable (i.e. <0.07 ng/ml). Scintigraphy showed a normally located thyroid gland with a goitre which was confirmed by ultrasound imaging. The right lobe measured 8.8 x 6.1 x 24 mm and the left lobe 9.5 x 5.9 x 20.5 mm. The baby was treated with l-thyroxine drops (35 ug per day). Her psychomotor development and growth were normal. Heterozygous for a previously documented nonsense mutation due to a cytosine to thymine transition at nucleotide 4588 in exon 22 (c.4588C > T, father's mutation) in one allele and for a novel also cytosine to thymine transition at nucleotide position 5386 in exon 27 (c.5386C > T, mother's mutation) in the other allele. The c.4588C>T and c.5386C>T mutations resulted in premature stop codons at amino acids 1511 [p.R1511X] and 1777 [p.Q1777X], respectively