Clinical and gene variation characteristic of 75 cases of hepatolenticular degeneration in children
10.16352/j.issn.1001-6325.2024.07.1008
- VernacularTitle:75例儿童肝豆状核变性的临床及基因变异特征
- Author:
Simin ZHANG
1
;
Wei WANG
;
Mingsheng MA
;
Zhengqing QIU
Author Information
1. 中国医学科学院 北京协和医学院 北京协和医院 儿科,北京 100730
- Keywords:
hepatolenticular degeneration;
clinical feature;
children;
ATP7B
- From:
Basic & Clinical Medicine
2024;44(7):1008-1012
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical characteristics of the hepatolenticular degeneration in children,and to clarify the significance of gene diagnosis in children with hepatolenticular degeneration.Methods A total of 75 patients with hepatolenticular degeneration were enrolled in the Department of Pediatrics,Peking Union Medical College Hospital from 2011 to 2018.All of them carried out a generation of gene sequencing for ATPase Cu2+trans-porting beta polypeptide(ATP7B)gene and multiplex ligation-dependent probe amplification(MLPA)analysis.Results Among the 75 pediatric patients,55 patients were asymptomatic and had elevated aminotransferases as the incidental findings.All the pediatric patients had decreased ceruloplasmin.Seventy-two of pediatric patients had 24-hour urinary copper＞40 μg/d.There were 16 cases that had Kayser-Fleischer(K-F)rings.Sixteen six out of 75(21.33%)cases were diagnosed clinically and 15 cases were＞7 years old.All the remaining patients needed genetic diagnosis.Sixty-six patients had two mutations and 9 patients had only one mutation,1 had no mutation.Forty eight different mutations were found to be localized in ATP7B gene.These mutations included 32 missense mutations,6 splice mutations,5 deletion mutations,2 repeated mutations,2 insert mutations and 1 nonsense muta-tions.The most frequently three mutations were c.2333G＞T,p.R778L,c.2621C＞T,p.A874V,c.2975C＞T,p.P992L,whose allele frequencies were 30.49%,14.89%,9.92%.Conclusions The research showed that in young aged patients,the nervous system symptoms are not obvious and the positive rate of laboratory tests are lower than adults so is a challenge to clinical diagnosis.So Genetic testing is of great significance for the early diagnosis and early treatment of disease in pediatric patients.
