Submicroscopic deletion involving the fibroblast growth factor receptor 1 gene in a patient with combined pituitary hormone deficiency

Endocrine Journal

Manami Iso¹  Itsuro Kazukawa⁴  Naoko Sato¹  Eiichi Kinoshita³  Sumito Dateki¹  Tsutomu Ogata¹  Maki Igarashi¹  Misuzu Seo²  Maki Fukami¹ 

[1] Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan;Department of Molecular Bioscience, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan;Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan;Department of Endocrinology, Chiba Children’s Hospital, Chiba 266-0007, Japan

关键词: Anterior pituitary;    Gonadotropin;    Gene deletion;    Copy-number;    Mutation;   

DOI  :  10.1507/endocrj.EJ13-0023

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(14)Cited-By(5)Combined pituitary hormone deficiency (CPHD), isolated hypogonadotropic hypogonadism (IHH), Kallmann syndrome (KS), and septo-optic dysplasia (SOD) are genetically related conditions caused by abnormal development of the anterior midline in the forebrain.Although mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been implicated in the development of IHH, KS, and SOD, the relevance of FGFR1 abnormalities to CPHD remains to be elucidated.Here, we report a Japanese female patient with CPHD and FGFR1 haploinsufficiency.The patient was identified through copy-number analyses and direct sequencing of FGFR1 performed for 69 patients with CPHD.The patient presented with a combined deficiency of GH, LH and FSH, and multiple neurological abnormalities.In addition, normal TSH values along with a low free T4 level indicated the presence of central hypothyroidism.Molecular analyses identified a heterozygous ~ 8.5 Mb deletion involving 56 genes and pseudogenes.None of these genes except FGFR1 have been associated with brain development.No FGFR1 abnormalities were identified in the remaining 68 patients, although two patients carried nucleotide substitutions (p.V102I and p.S107L) that were assessed as benign polymorphism by in vitro functional assays.These results indicate a possible role of FGFR1 in anterior pituitary function and the rarity of FGFR1 abnormalities in patients with CPHD.

【 授权许可】

Unknown