Identification of one novel and nine recurrent mutations of the ATP7B gene in 11 children with Wilson disease

Juan Geng, Jian Wang, Ru-En Yao, Xiao-Qing Liu, Qi-Hua Fu

Shanghai, China

Author Affiliations: Department of Laboratory Medicine (Geng J, Yao RE, Fu QH), Division of Birth Defects Research, Institute of Pediatric Translational Medicine (Wang J, Fu QH), and Department of Pediatric Internal Medicine (Liu XQ), Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China

Corresponding Author: Qi-Hua Fu, PhD, Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine. 1678 Dongfang Road, Shanghai 200127, China (Tel: +86-21-38625568; Fax: +86-21-58756923; Email: qfu@shsmu.edu.cn)

doi: 10.1007/s12519-012-0388-7

Background: Wilson disease (WND), also called hepatolenticular degeneration, is an autosomal recessive genetic disorder in which copper abnormally accumulates in several organs. WND arises from the defective ATP7B gene, which encodes a copper transporting P-type ATPase.

Methods: The molecular defects in 11 unrelated Chinese WND patients aged from 3 to 12 years were investigated. The diagnosis of these patients was based on typical clinical symptoms and laboratory testing results. All 21 exons and exon-intron boundaries of the ATP7B gene were amplified by polymerase chain reaction from the genomic DNA of the patients and then analyzed by direct sequencing. One hundred healthy subjects served as controls to exclude gene polymorphism.

Results: In one novel (c.3605 C>G) and nine recurrent mutations of ATP7B identified, there were eight missense mutations, one splice-site mutation, and one nonsense mutation. The novel c.3605 C>G mutation resulted in the substitution of alanine by glycine at amino acid position 1202 (p.Ala1202Gly). The most frequent ATP7B mutation was c.2333 G>T (p.Arg778Leu), followed by c.2975 C>T (p.Pro992Leu), which accounted for 63.6% of the WND mutated alleles.

Conclusions: The novel c.3605 C>G mutation in ATP7B is one of the molecular mechanisms of WND.

Key words: ATP7B; gene; mutation; Wilson disease

World J Pediatr 2013;9(2):158-162