TTC1遺伝子におけるp.Phe262Valホモジゴス変異と関連したポント・セレベラー・ヒポプラシアと周室性白血病: 4件の報告
Gamze Sarıkaya Uzan1,2, Ali Han Yaramış3, Ece Sönmezler4
1Division of Child Neurology, Department of Pediatrics, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
まとめ
4人の女性患者において,遺伝子分析により,ポント・セレベラ・ヒポプラシア (PCH) と周周周白内障症に関連したTTC1遺伝子変異が特定されました. この発見はTTC1を先天性脳異常に結びつけ,PCH診断の候補遺伝子として示唆しています.
科学分野:
- 遺伝学
- 神経発達障害
- 医学 研究
背景:
- Pontocerebellar hypoplasia (PCH) は,多数のサブタイプを持つ稀な神経発達障害のグループである.
- TTC1遺伝子は,これまでOMIMデータベースの臨床的フェノタイプと関連付けられていなかった.
- この研究は,TTC1遺伝子とPCHの間の潜在的なリンクを調査しています.
研究 の 目的:
- 4人の患者のPCHの遺伝的原因と関連する臨床的特徴を特定する.
- TTC1遺伝子が 生まれつきの脳異常に 関与しているかどうか
- PCH遺伝子評価のための候補遺伝子としてTTC1を提案する.
主な方法:
- 感染した個人とその家族に対して全エクソムの配列解析を行った.
- 変種優先順位は RD-Connect ゲノム・フェノム分析プラットフォームを使用して行われました.
- TTC1遺伝子 (c.784T>G,p.Phe262Val) の同位体のミッセンスの変異は,感染した個体で確認された.
主要な成果:
- 2つの家族から4人の女性患者がPCH,全身発達遅延,小頭症,周周性白血病を発症しました.
- 特定されたTTC1変種 (p. Phe262Val) は,感染した個体においてホモジゴスであり,感染していない親および兄弟姉妹においてヘテロジゴスであった.
- この変種はClinVarで病原性可能性として分類され,観察された表型との関連が確認されています.
結論:
- TTC1遺伝子変異体 (p. Phe262Val) はPCHと脳辺縁白血病に関連しています.
- これはTTC1と先天性脳異常を 関連付ける最初の報告です
- TTC1は,PCHおよび関連する脳異常の遺伝子診断に考慮されるべきです.
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