Investigation of pathology and development of specific medial care system and treatment associated with FLNA deficiency

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860796
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kyoto University
• Principal Investigator: Kawai Tomoki 京都大学, 医学(系)研究科(研究院), 助教 (20631568)
• Co-Investigator(Renkei-kenkyūsha): Ohara Osamu 理化学研究所, 免疫ゲノミクス研究グループ, グループディレクター (20370926) ; Suzuki Hidenori 日本医科大学, 形態解析共同研究施設, 准教授 (30158977) ; Kunishima Shinji 国立病院機構名古屋医療センター, 高度診断研究部分子診断研究室, 室長 (60373495) ; Oda Hirotsugu 田附興風会, 医学研究所北野病院小児科, 副部長 (20772239) ; Hiejima Eitaro 京都大学, 医学部附属病院小児科, 医員 (60773520)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: FLNA / エキソンスキップ

Outline of Final Research Achievements

Loss-of-function mutations in FLNA cause variable multiple organ complications in females and are typically lethal to males. This study investigated familial male cases with a loss-of-function mutation in FLNA who showed atypical mild clinical courses. A 4 bp deletion in exon 40 was detected, which was predicted to cause a lethalpremature protein truncation in the patietns. However, intrinsic induced in-frame skipping of the mutated exon led to the translation of a mutant FLNA missing an internal region of 41 amino acids. The exon-skipped FNLA protein was revealed to restore partially its function comparable to the wild type FLNA. The present study expands the diversity of the phenotypes associated with loss-of-function mutations in FLNA and indicated induction of exon skipping could be a theraupic option. In additon, this study indicated the usefulness of rapid daignosis using FLNA immmunnostaining of platelets.

Free Research Field

小児科学