Objective: The present study was aimed at exploring the mutation profile of Eastern Indian Wilson’s Disease (WD) patients and analyzing the effect of mutations by genotype phenotype correlation.

Background: WD is an autosomal recessive disease caused by mutation in the ATP7B gene.More than 400 disease causing mutations have been identified. Clinical manifestations of WD are variable, even differing among persons carrying the same homozygous mutation. Identification of the prevalent mutations in a given population is necessary to provide mutation-based molecular diagnosis. Previous studies have detected common mutations in this part of the world and our study aims to correlate genotype with clinical features and radiological features

Method: A descriptive cross sectional observational study was conducted over a period of two years in a tertiary care hospital and neurology referral unit of Kolkata, India. All WD patients within the study period and meeting the inclusion criteria were included . Demographic data collection, clinical examination and relevant laboratory investigations were done. Magnetic resonance imaging of brain, and cognitive assessment by Mini Mental Score Exam (MMSE) were also performed. Blood was collected for genetic analyses. PCR-Sanger sequencing of exons 2,4,8,14,18 and 19 of ATP7B gene was done based on previous reports of mutation hotspots of ATP7B gene for WD in Eastern India.

Results: 34 WD patients were included in the study, 55.9% of whom were males. The median age was 16.5 years (range 10-38 years) while the median age at diagnosis was 12 years (range 5-31 years). Majority (21/34, 61.8%) of the patients had dystonia on presentation, followed by dysarthria (41.2%), tremor (17.6%) and ataxia (11.8%). The median MMSE score in the study population was 24 (IQR 22-25.5). Both mutations were detected in 11 (32.4%) patients, all of whom were compound heterozygotes, while a single mutation was found in 14 (41.2%) patients. No likely pathogenic mutation was detected in 9 patients. c.813C>A (p.C271X) was the commonest identified mutation, representing 30.6% of all characterized coding mutant alleles.

Conclusion: WD patients in eastern India have significant genotypic and phenotypic diversity. Further studies with larger samples and screening of remaining exons are warranted .

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-study-of-mutation-in-atp7b-gene-and-its-correlation-with-clinical-phenotype-and-radiological-features-in-patients-of-wilson-disease-a-population-based-study-in-a-tertiary-care-institute-in-eastern-i/