Figure 1. Clinical features and genetic studies of the patient with IGSF1 deletion.

(A) Picture of the 14 day-old-patient with severe phenotype of hypothyroidism including facial myxedema and protruding tongue. The boy was born to a phenotypically normal father and a euthyroid mother with low TSH. (B) TRH stimulation test at 3 years of age. Low TSH response (peak = 3.2 mIU/L) and normal prolactin response consistent with pituitary defect⁶⁸. (C) GnRH test at 6 years of age. Abnormal over-stimulation of FSH and LH and unresponsive testosterone without development of clinical signs of precocious puberty, excepting macroorchidism⁶⁹. (D) CGH-Array showing the deletion of 207 Kb in Xq26 including the IGSF1 gene. (E) PCR-amplified DNA fragments using primers on the flanking regions of the deletion in non-carrier father, heterozygous mother and hemizygous patient. A band of around 3 Kb is amplifiable when the deletion is present. Precise break-point of deletion as sequenced in PCR fragments from mother and patient. (F) TSH bioactivity of patient’s serum at the age of 14 (red) in relation to standard rhTSH (black): (a) patient’s serum under L-T4; (b) patient’s serum after four weeks of levo-thyroxine withdrawal; (c) patient’s serum after TRH stimulation test. Three dilutions for each condition are shown: 1:2, 1:4 and 1:8. CCH: central congenital hypothyroidism, min: minutes, TSH: thyrotropin, PRL: prolactin, FSH: follicle-stimulating hormone, Testost.: testosterone, GnRH: gonadotropin-releasing hormone, rhTSH: recombinant human TSH, L-T4: levothyroxine treatment, TRH stim.: TRH stimulus, RRR: Relative Response Ratio.