<abstract xmlns="http://www.w3.org/1999/xhtml"><p> Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene. Objective: Report the clinical data and mutation analysis of two Thai siblings suspected of WD. Subject and methods: A 13-year-old boy who presented with cirrhosis, arthralgia, hypoalbuminemia, and coagulopathy, and his 11-year-old sister who was asymptomatic but had hepatomegaly with elevation of transaminases, were studied. Mutation analysis of ATP7B gene and mRNA analysis was performed in both patients and their parents. Results: Investigations were consistent with WD, and their liver diseases improved after standard treatment for WD. DNA analyses in these two patients revealed two novel mutations, which were a deletion of the first 2bp of exon 6 (c.1870_1871delGA), and a single base substitution from A to G at nucleotide 4075 (c.4075A>G) in the exon 20 (p.M1359V). PCR-restriction digestion with NcoI restriction enzyme was employed as the second method for confirmation of the c.4075A>G mutation and for rapid screening in 100 chromosomes from unrelated healthy controls, and this variant was not present in the controls. The c.1870_1871delGA deletion caused a frameshift effect, which results in a premature stop codon (p.E624fsX753), and the p.M1359V mutation is a substitution of methionine with valine, which may have effects upon its orientation and interaction with other adjacent amino acids. Conclusion: Two novel mutations of ATP7B gene were identified in two Thai siblings with WD.</p></abstract>

Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene. Objective: Report the clinical data and mutation analysis of two Thai siblings suspected of WD. Subject and methods: A 13-year-old boy who presented with cirrhosis, arthralgia, hypoalbuminemia, and coagulopathy, and his 11-year-old sister who was asymptomatic but had hepatomegaly with elevation of transaminases, were studied. Mutation analysis of ATP7B gene and mRNA analysis was performed in both patients and their parents. Results: Investigations were consistent with WD, and their liver diseases improved after standard treatment for WD. DNA analyses in these two patients revealed two novel mutations, which were a deletion of the first 2bp of exon 6 (c.1870_1871delGA), and a single base substitution from A to G at nucleotide 4075 (c.4075A>G) in the exon 20 (p.M1359V). PCR-restriction digestion with NcoI restriction enzyme was employed as the second method for confirmation of the c.4075A>G mutation and for rapid screening in 100 chromosomes from unrelated healthy controls, and this variant was not present in the controls. The c.1870_1871delGA deletion caused a frameshift effect, which results in a premature stop codon (p.E624fsX753), and the p.M1359V mutation is a substitution of methionine with valine, which may have effects upon its orientation and interaction with other adjacent amino acids. Conclusion: Two novel mutations of ATP7B gene were identified in two Thai siblings with WD.

Mutations of ATP7B gene in two Thai siblings with Wilson disease

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"Mutations of ATP7B gene in two Thai siblings with Wilson disease"}

Background: Wilson disease (WD) is an autosomal recessive disorder of copper metabolism caused by mutations in ATP7B gene. Objective: Report the clinical data...

Mutations of ATP7B gene in two Thai siblings with Wilson disease

Publié en ligne: 13 avr. 2018

Pages: 163 - 169

DOI: https://doi.org/10.2478/abm-2010-0020

Mots clés
ATP7B gene, cirrhosis, liver disease, Wilson disease

© 2018

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mutations of ATP7B gene in two Thai siblings with Wilson disease

Publié en ligne: 13 avr. 2018

Pages: 163 - 169

DOI: https://doi.org/10.2478/abm-2010-0020

Mots clésATP7B gene, cirrhosis, liver disease, Wilson disease

© 2018

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Mots clés
ATP7B gene, cirrhosis, liver disease, Wilson disease