Protein trung tâm I (CENPI) là một gen ứng cử cho hội chứng thận nhiễm mỡ nhạy cảm với steroid liên quan đến nhiễm sắc thể X

Springer Science and Business Media LLC - Tập 33 - Trang 763-769 - 2020
Sulman Basit1, Howaida Mohammed Al-Edressi2, Mona Hamza Sairafi2, Jamil Amjad Hashmi1, Essa Alharby1, Ramzia Safar2, Khushnooda Ramzan3
1Center for Genetics and Inherited Diseases, Taibah University Almadinah Almunawwarah, Medina, Kingdom of Saudi Arabia
2Department of Nephrology, Madinah Maternity and Children Hospital, Medina, Kingdom of Saudi Arabia
3Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia

Tóm tắt

Những cá nhân có protein niệu đi kèm với hạ albumin huyết, phù nề và tăng lipid máu được coi là mắc hội chứng thận nhiễm mỡ (NS). NS là bệnh thận phổ biến nhất gặp ở nhóm tuổi nhi. NS thường được phân loại thành hội chứng thận nhiễm mỡ kháng steroid (SRNS) và hội chứng thận nhiễm mỡ nhạy cảm với steroid (SSNS). Hơn 58 gen đã được xác định là nguyên nhân đơn gen của SRNS; tuy nhiên, cấu trúc di truyền của SSNS ở trẻ em vẫn chưa được hiểu rõ. Trong nghiên cứu này, chúng tôi đã thực hiện giải trình tự 66 gen ứng cử về NS, tiếp theo là định gen SNP toàn bộ bộ gen và giải trình tự toàn bộ exome ở các gia đình SSNS với nhiều cá nhân bị ảnh hưởng. Giải trình tự các gen ứng cử về NS không phát hiện biến thể gây bệnh nào ở các gen đã biết. Lập bản đồ đồng hợp tử dựa trên mô hình lặn tự nhiễm thất bại trong việc phát hiện bất kỳ vùng mất dị hợp tử chung nào trong bộ gen. Phân tích dữ liệu exome không thiên lệch và không dự đoán đã xác định được một biến thể sai mã (c.383G>A; p.Arg128Gln) trong gen CENPI. Giải trình tự Sanger của cả hai bậc phụ huynh, cá nhân không bị ảnh hưởng và cá nhân bị ảnh hưởng đã xác nhận một mẫu di truyền liên kết với nhiễm sắc thể X của biến thể (c.383G>A) với kiểu hình SSNS. Biến thể (c.383G>A) rất hiếm và có khả năng gây hại. Tập hợp lại, những quan sát này gợi ý rằng có một liên kết gây bệnh đặc biệt giữa sự phát triển của SSNS và sự thay đổi trong CENPI. Tuy nhiên, các đột biến ở người trong CENPI gây ra SSNS chưa được báo cáo cho đến nay. Việc xác định các khiếm khuyết di truyền gây ra SSNS sẽ giúp hiểu rõ hơn về nguyên nhân chính xác của SSNS và cải thiện quản lý trẻ em mắc NS.

Từ khóa

#hội chứng thận nhiễm mỡ #gen CENPI #di truyền học #bệnh thận #trẻ em #không nhạy cảm với steroid #di truyền liên kết với nhiễm sắc thể X

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