A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling

Kentaro Suda, Hidenori Fukuoka, Genzo Iguchi, Keitaro Kanie, Yasunori Fujita, Yukiko Odake, Ryusaku Matsumoto, Hironori Bando, Hiroki Ito, Michiko Takahashi, Kazuo Chihara, Hiroshi Nagai, Satoshi Narumi, Tomonobu Hasegawa, Wataru Ogawa, Yutaka Takahashi

研究成果: Article査読

抄録

Context: Luscan-Lumish syndrome (LLS) is characterized by postnatal overgrowth, obesity, Chiari I malformation, seizures, and intellectual disability. SET domain-containing protein 2 (SETD2) is a histone methyltransferase, where mutations in the gene are associated with the development of LLS. However, mechanisms underlying LLS remain unclear. Case Description: A 20-year-old man was referred to our hospital because of tall stature. His body height was 188.2 cm (+3.18 SD) and he showed obesity with a body mass index of 28.4 kg/m2. He exhibited acral overgrowth, jaw malocclusion, and prognathism, but no history of seizures, intellectual disability, or speech delay. Serum growth hormone (GH), insulin-like growth factor 1 (IGF-1), and nadir GH levels after administration of 75 g oral glucose were within normal range. Pituitary magnetic resonance imaging showed no pituitary adenoma, but Chiari I malformation. Whole exome sequencing analysis of the proband revealed a de novo heterozygous germline mutation in SETD2 (c.236T>A, p.L79H). Skin fibroblasts derived from the patient grew faster than those from his father and the control subject. In addition, these cells showed enhanced tyrosine phosphorylation and transcriptional activity of signal transducer and activator of transcription 5b (STAT5b) and increased IGF-1 expression induced by GH. Conclusion: This is a mild case of LLS with a novel mutation in SETD2 without neurological symptoms. LLS should be differentiated in a patient with gigantism without pituitary tumors. Although further investigation is necessary, this is the first study to suggest the involvement of aberrant GH signaling in the development of LLS.

本文言語English
ページ(範囲)718-723
ページ数6
ジャーナルJournal of Clinical Endocrinology and Metabolism
106
3
DOI
出版ステータスPublished - 2021 3 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

フィンガープリント 「A Case of Luscan-Lumish Syndrome: Possible Involvement of Enhanced GH Signaling」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル