tailieunhanh - Ứng dụng kỹ thuật sinh học phân tử trong chẩn đoán bệnh Wilson và sàng lọc người mang gen bệnh

Bệnh Wilson (WD) là bệnh di truyền lặn trên NST thường do đột biến gen ATP7B. Sự lắng đọng đồng trong gan, não và một số cơ quan khác của cơ thể do rối loạn cơ chế vận chuyển và bài tiết đồng do đột biến gen ATP7B là nguyên nhân của của nhiều bệnh lý phức tạp liên quan đến gan và não. Chẩn đoán xác định bệnh WD sẽ giúp trẻ được điều trị hiệu quả. | Journal of Pediatric Research and Practice Vol. 4 No. 5 2020 10-20 Research Paper Application of Biotechnology in Detection ATP7B Gene Mutation in Vietnamese Children with Wilson Disease and Screening Target Mutation for Their Family Members Nguyen Thi Mai Huong Nguyen Pham Anh Hoa Ngo Diem Ngoc Vietnam National Children s Hospital 18 879 La Thanh Dong Da Hanoi Vietnam Received 12 August 2020 Revised 22 August 2020 Accepted 28 August 2020 Abstract Background Purpose Wilson s disease WD is an autosomal recessive disorder of the copper metabolism which is caused by a mutation in the copper-transporting P- type ATPase ATP7B . The mechanism of this disease is the failure of hepatic excretion of copper to bile and leads to copper deposits in the liver and other organs. The ATP7B gene is located on the long arm of chromosome 13 . This study aimed to investigate the gene mutation in the Vietnamese patients with WD and make a asymptomatic diagnosis for their familial members. Methods Forty-three WD patients and their 67 siblings were identified as having ATP7B gene mutations. Genomic DNA was extracted from peripheral blood samples 21 exons and exon-intron boundaries of the ATP7B gene were analyzed by direct sequencing. Results A total of 27 different mutations were detected in this study which accounted for . Of which S105 was the most prevalent mutation accounting for . Following was the five other mutations including I1148T IVS14-2A gt G L1371P T850I and V176SfsX28 . Among 47 genotypes ratio of compound heterozygote was . Most of the mutations in the study occurred in exon 2 exon 16 exon 8 exon 14 and intron 14 . A total of 13 affected siblings were identified by target mutation on ATP7B gene which was identified in the proband. Among them 5 cases were asymptomatic that would be treated soon to prevent clinical feature. This study also discoved 65 carriers in their family members. Conclusion The findings highest .