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

• Fukami Maki

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan

• Iso Manami

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan

• Sato Naoko

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan

• Igarashi Maki

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan

• Seo Misuzu

  Department of Molecular Bioscience, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan

• Kazukawa Itsuro

  Department of Endocrinology, Chiba Children’s Hospital, Chiba 266-0007, Japan

• Kinoshita Eiichi

  Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan

• Dateki Sumito

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8501, Japan

• Ogata Tsutomu

  Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo 157-8535, Japan Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan

書誌事項

タイトル別名

• Submicroscopic deletion involving the <i>fibroblast growth factor receptor 1</i> gene in a patient with combined pituitary hormone deficiency

抄録

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.

収録刊行物

• Endocrine Journal

  Endocrine Journal 60 (8), 1013-1020, 2013

  一般社団法人 日本内分泌学会

キーワード

• Anterior pituitary
• Gonadotropin
• Gene deletion
• Copy-number
• Mutation

詳細情報

• CRID: 1390282681276319872
• NII論文ID: 10031195771
• NII書誌ID: AA10901436
• DOI: 10.1507/endocrj.ej13-0023
• COI: 1:STN:280:DC%2BC3snhvV2nuw%3D%3D
• ISSN: 13484540
• ISSN: 09188959
• PubMed: 23657145
• Web Site: https://www.jstage.jst.go.jp/article/endocrj/60/8/60_EJ13-0023/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014164060
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可