Objective: To characterize the phenotypic and genotypic spectra in Wilson disease (WD) and to investigate the relationships between the neurological and hepatic phenotypes and the multiple disease-causing mutations in the ATP7B gene.

Background: WD is an autosomal recessive disorder due to mutations in the ATP7B gene impairing the copper transport. WD is characterized by a spectrum of clinical presentations. We hypothesized that this phenotypic variability could potentially be associated with variants grouped by functional of the ATP7B protein

Method: We performed a systematic literature review from 1993 to 2018 for publications on phenotype-genotype correlations in WD. From 4,664 entries, we extracted individual-patient data (IPD) from 1,417 subjects with symptomatic WD from 53 studies. Reported variants for both alleles were ascertained in 1,037 subjects. Variants were categorized as related to ATP-binding, copper-binding, transmembrane or unknown domains. Random-effects meta-analyses of single proportions and meta-regression were performed

Results: Neurologic phenotype was reported in 54% (95%CI: 44–63%, n=604) of the population with an estimated mean age of onset of 18.7 years (95%CI: 16.2–21.3), while the hepatic phenotype(n=433) started at younger mean age (13.9 years, 95%CI: 11.9–15.9). We identified five patients with isolated psychiatric symptoms and 37 with concomitant brain and hepatic symptoms, who were excluded from further analysis. Significant heterogeneity was seen across studies. There was no significant difference in the proportion of neurological phenotype across domains; however, variants affecting the transmembrane domain tend to have a lower proportion of neurological phenotype

Conclusion: This study provides a comprehensive and up‐to‐date review of the published peer‐reviewed literature on phenotype-genotype correlations in WD. We did not find any significant association in between mutations affecting particular functional domains and any specific phenotype

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/wilson-disease-a-systematic-review-and-meta-analysis-in-phenotype-genotype-correlations/