Liver disease phenotypes and clinical features of patients with different genotypes of Wilson’s disease
- VernacularTitle:肝豆状核变性不同基因型患者的肝病表型及临床特征分析
- Author:
Yuanzhi HUANG
1
;
Fuchuan WANG
2
;
Yi DONG
2
;
Zhiqiang XU
2
;
Yinjie GAO
2
;
Jianguo YAN
2
;
Lili CAO
2
;
Danni FENG
2
;
Min ZHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: Hepatolenticular Degeneration; Genotype; Phenotype
- From: Journal of Clinical Hepatology 2024;40(8):1627-1632
- CountryChina
- Language:Chinese
- Abstract: ObjectiveTo investigate the liver disease phenotypes and clinical features of patients with different genotypes of Wilson’s disease （WD）. MethodsA retrospective analysis was performed for 163 patients with WD who were diagnosed and underwent genetic testing in The Fifth Medical Center of Chinese PLA General Hospital from August 2008 to June 2023， and clinical manifestations， laboratory examination， pathological examination， imaging examination， and ATP7B genetic testing results were collected. According to ATP7B gene mutation， the patients were divided into groups as follows： R778L mutation group and non-R778L mutation group； P992L mutation group and non-P992L mutation group； truncation mutation group and non-truncation mutation group. Liver disease phenotypes and clinical features were analyzed for the patients with c.2333G>T/p.R778L mutation （R778L mutation）， c.2975C>T/p.P992L mutation （P992L mutation）， and truncation mutation of the ATP7B gene. The Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of continuous data between groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsThe 163 patients with WD had varying severities of liver disease phenotypes， among whom 121 （74.23%） were diagnosed with chronic liver disease， 36 （22.09%） were diagnosed with decompensated cirrhosis， and 6 （3.68%） were diagnosed with fulminant WD， and in addition， there were 5 patients （2 with chronic liver disease and 3 with decompensated cirrhosis） with neurological abnormalities. For the 163 patients with WD， R778L mutation （with an allele frequency of 28.2%） was the most common mutation in the ATP7B gene， followed by P992L mutation （with an allele frequency of 12.6%）， and truncation mutation showed an allele frequency of 11.0%. There was no significant difference in the distribution of the three mutations across different liver disease phenotypes （P>0.05）. The R778L mutation group had a significantly lower level of ceruloplasmin （CP） than the non-R778L mutation group ［0.04 （0.02 — 0.08） g/L vs 0.08 （0.03 — 0.13） g/L， Z=-2.889， P=0.004］. Compared with the non-P992L mutation group， the P992L mutation group had significantly higher levels of alanine aminotransferase ［135.0 （80.5 — 237.0） U/L vs 80.5 （36.0 — 173.3） U/L， Z=2.684， P=0.007］ and aspartate aminotransferase ［121.4 （77.0 — 195.0） U/L vs 84.0 （39.0 — 123.3） U/L， Z=3.388， P<0.001］. Compared with the non-truncation mutation group， the truncation mutation group had significantly lower levels of CP ［0.03 （0.02 — 0.08） g/L vs 0.06 （0.03 — 0.11） g/L， Z=-3.136， P=0.002］ and serum copper ［3.20 （2.15 — 5.00） mg/L vs 4.20 （2.60 — 7.50） mg/L， Z=-2.296， P=0.025］. ConclusionR778L mutation， P992L mutation and truncation mutation are not associated with liver disease phenotype in WD patients； however， R778L mutation is associated with a lower level of CP， P992L mutation is associated with higher levels of ALT and AST， and truncation mutation is associated with lower levels of CP and serum copper.
