Mlecular analysis of epigenetic disorders including pseudohypoparathyroidism

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461392
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Department of Clinical Research, National Hospital Organization Kyoto Medical Center
• Principal Investigator: Usui Takeshi 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 客員室長 (20271512)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 偽性副甲状腺機能低下症

Outline of Final Research Achievements

To clarify the usefulness of methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), we evaluated genetic and epigenetic changes of the GNAS locus in Japanese PHP-Ib patients.
We studied 13 subjects with PHP-Ib (three families with eight affected members and one unaffected member and four sporadic cases). The methylation status of GNAS differentially methylated regions (DMRs) was evaluated using MS-MLPA. The main outcome measure was the presence of deletion mutations in the GNAS locus and STX16, which were assessed using MLPA. In all familial PHP-Ib cases, a 3kb deletion of STX16 and demethylation of the A/B domain were identified. In contrast, no deletion was detected throughout the entire GNAS locus region in the sporadic cases. Broad methylation abnormalities were observed in the GNAS DMRs.

Free Research Field

内分泌学