An international collaboration involving Dr Nadia Schoenmakers and Krishna Chatterjee at the University of Cambridge Metabolic Research Laboratories, and scientists from McGill University and researchers in The Netherlands, Italy and Australia have discovered that mutations in a gene called immunoglobulin superfamily member-1 (IGSF-1) cause thyroid hormone deficiency due to ineffective signalling via the thyrotropin-releasing hormone receptor (TRHR) in the pituitary gland. The disorder is X-linked, but many affected individuals remain undiagnosed; accordingly, genetic testing and ascertainment of cases is likely to be of clinical benefit. The disorder is also associated with testicular enlargement and the mechanism for this remains to be elucidated.
The study is published in the following article: Loss-of-function mutations in IGSF1 cause a novel X-linked syndrome of central hypothyroidism and testicular enlargement. Sun Y*, Bak B*, Schoenmakers N*, van Trotsenburg ASP*, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SNM, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TME, Hokken-Koelega ACS, Del Blanco DG, Rangasami JJ, Ruivenkamp CAL, Laros JFJ, Kriek M, Kant SG, Bosch CAJ, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GCJ, Pereira AM, den Dunnen JT, Wade MG, Breuning MH, Hennekam RC, Chatterjee K†, Dattani MT†, Wit JM†, Bernard DJ†. Nature Genetics (2012) DOI: 10.1038/ng.2453 (*coequal first authors; † coequal corresponding authors)