Genetic analysis of HPMR syndrome

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Tohoku University
• Principal Investigator: Fujiwara Ikuma 東北大学, 医学(系)研究科(研究院), 教授 (10271909)
• Co-Investigator(Kenkyū-buntansha): KANNO Junko 東北大学, 大学病院, 講師 (30509386) ; HAKODA Akiko 東北大学, 大学院医学系研究科, 非常勤講師 (70509398)
• Co-Investigator(Renkei-kenkyūsha): NIIHORI Tetsuya 東北大学, 大学院医学系研究科, 准教授 (40436134)
• Research Collaborator: MURAKAMI Yoshiko
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 高アルカリフォスファターゼ血症 / GPI / 発達遅滞 / Mabry症候群 / HPMR症候群 / 全エクソンシークエンス

Outline of Final Research Achievements

We found two heterozygous frameshift mutations in PIGL gene in a patient with Mabry syndrome, or hyperphosphatasia mental retardation syndrome (HPMRS) by whole-exome sequencing. Surface expression of the glycosylphosphatidylinositol (GPI)-anchored proteins, such as DAF, FLARE, CD24 and CD16, were decreased both in granulocytes from the patient and PIGL-deficient CHO cells expressing the mutated cDNA.
Nonsynonymous changes or frameshift mutations in PIGL have been identified in patients with CHIME syndrome. These results suggest that frameshift mutations that result in premature termination in PIGL cause a phenotype that is consistent with HPMRS.

Free Research Field

小児内分泌学