A novel mutation of IGSF1 in a Japanese patient of congenital central hypothyroidism without macroorchidism.
Congenital central hypothyroidism (C-CH) is a rare disease known to be caused by mutations of the genes encoding TSH β or the TRH receptor gene, although the cause of the disease in a number of patients has not yet been clarified. Recently, mutations and deletions of the immunoglobulin superfamily member 1 (IGSF1) gene have been reported to be the cause of C-CH. Here we report a Japanese male patient with C-CH due to a novel IGSF1 mutation. He was detected by neonatal mass screening of simultaneous TSH and free T4 measurements and levothyroxine was initiated. At 6 years of age he underwent ¹²³I scintigraphy after levothyroxine treatment had been discontinued for one month and his thyroid and pituitary function were evaluated. Since TSH and PRL responses after TRH stimulation were low, his diagnosis of C-CH was confirmed. During follow up, whereas onset of his puberty was delayed, his secondary sex characterization completed at 17 years old. In this patient we analyzed IGSF1 and TRHR. As results, we identified a novel insertion mutation in IGSF1 (c.3528-3529insC), resulting in a premature stop codon (p.Pro1082Trpfs39X). In conclusion, we identified a novel mutation of IGSF1 in a Japanese male patient with C-CH.
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo 060-8635, Japan. tajeari@med.hokudai.ac.jp
Toshihiro
T
Tajima
Akie
A
Nakamura
Katsura
K
Ishizu
D000293:Adolescent; D041923:Adolescent Development; D002648:Child; D002657:Child Development; D018389:Codon, Nonsense; D003409:Congenital Hypothyroidism / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005091:Exons; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016254:Mutagenesis, Insertional; D009154:Mutation; D010902:Pituitary Gland / Q000503:physiopathology; D013961:Thyroid Gland / Q000503:physiopathology
D018389:Codon, Nonsense; C112314:IGSF1 protein, human; D007136:Immunoglobulins; D008565:Membrane Proteins