Molecular and Cellular Biochemistry 294: 1–10, 2007. DOI: 10.1007/s11010-005-9028-z c ❣ Springer Analysis of most common mutations R778G, R778L, R778W, I1102T and H1069Q in Indian Wilson disease patients: Correlation between genotype/phenotype/copper ATPase activity Sandeep Kumar, 1 Baburam Thapa, 2 Gurjit Kaur 3 and Rajendra Prasad 1 1 Department of Biochemistry; 2 Department of Pediatric Gastroenterology, Advance Pediatric Center, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India; 3 Department of Physiology, Government Medical College, Chandigarh 160032, India Received 1 September 2005; accepted 7 October 2005; Published online: 8 December 2006 Abstract The present study was intented to estimate the frequencies of the most common mutations (R778L, R778W, R778G, I1102T and H1069Q) of ATP7B in Indian Wilson disease (WD) population and to explore the correlation between genotype/phenotype and copper ATPase activity. A total of 33 WD patients and their family members from North West states of India were examined. The H1069Q, R778W and R778L mutations were absent in these WD patients. R778W and I1102T mutations were present in 36% of WD patients. Family analysis for these mutations using PCR-RFLP documented 5 carriers and 2 asymptomatic WD patients. The copper ATPase activity in WD patients was significantly reduced (50%) than that of control individuals. No significant difference was observed in copper stimulated ATPase activity between homozygous (R778W/R778W, I1102T/I1102T) and compound heterozygous (R778W/unknown mutation, I1102T/unknown mutation) WD patients. Serum ceruloplasmin, serum copper levels were significantly lower in homozygous WD patients than that of compound heterozygous. However, no significant difference was observed in liver copper contents between heterozygous and homozygous patients. In conclusion, the data suggest that R778W and I1102T are most common mutations and provide the basis of genetic (PCR-RFLP) diagnostic tool for Indian WD patients as well as in siblings/parents where biochemical parameters are ambiguous. (Mol Cell Biochem 294: 1–10, 2007) Key words: ATP7B gene mutation, H1069Q, I1102T, R778G, R778L, R778W, restriction fragment length polymorphism, seminested polymerase chain reaction, Wilson disease Introduction Wilson Disease (WD, MIM#27790) is one of the typical error of copper metabolism caused by autosomal recessive heredity. The causal gene “ATP7B” is located at 13q14.3 [1–3]. WD is characterized by dysfunction of this gene, which causes abnormal accumulation of copper in various tissues, Address for offprints: R. Prasad, Department of Biochemistry, PGIMER, 160012, Chandigarh, India (E-mail: feteh1977@yahoo.com) such as liver, basal ganglia, kidney and cornea. Major clinical manifestations are chronic liver disease and/or neurological impairment, frequently along with kidney malfunction and hemolysis [4]. WD has a worldwide prevalence of between 1 in 35000 and estimated carrier frequencies of 1 in 90. With the declining incidence of Indian Childhood Cirrhosis (ICC) and other metabolic liver disorders, WD has become one of the 2006