https://pubmed.ncbi.nlm.nih.gov/36112267/ Wilson disease

Indian J Pediatr. 2022 Sep 16.
doi: 10.1007/s12098-022-04250-9. Online ahead of print.

Genomic Variations in ATP7B Gene in Indian Patients with Wilson Disease

Aabha Nagral 1 2 3, Snehal Mallakmir 4, Nikita Garg 5, Kritika Tiwari 6, Suzena Masih 7, Nishtha Nagral 8, Ojas Unavane 9, Ajay Jhaveri 5, Shubha Phadke 7, GaneshPrasad ArunKumar 10, Rakesh Aggarwal 11 12
Affiliations expand
PMID: 36112267

DOI: 10.1007/s12098-022-04250-9

Abstract
Objective: To report genotype data of the patients with Wilson disease (WD) hailing from across several parts of India to add to the available spectrum of causative variants in ATP7B gene (ATPase copper transporting beta polypeptide gene) and associated phenotypes in the Indian population.
Methods: The entire ATP7B gene was sequenced in 58 patients with WD and additional testing was also done by MLPA to look for intragenic deletions duplications and exome sequencing to rule out genetic variations with similar phenotypic overlap.

Results: Of all patients, 37 patients had a total of 33 distinct pathogenic variations, including 29 in the exonic regions and 4 at intronic splice sites. Of the variations identified, six were novel. The underlying genomic variations could be identified in nearly two-thirds of the patients by sequencing the entire gene.

Conclusions: This study reports the genotype-phenotype data to add to the available spectrum of causative variants in ATP7B gene. The inability to detect a pathogenic variation in some patients and the existence of phenotypic variations in individuals with the same variation suggest that additional factors or genes may play a role in causation of the disease. Further, a marked genetic heterogeneity was found in the study patients, indicating ethnic diversity of the Indian population.