[Mutation analysis of 35 Wilson's disease pedigrees]

Area of Science:

• Genetics
• Molecular Biology
• Medical Diagnostics

Background:

• Wilson disease is a genetic disorder caused by mutations in the ATP7B gene.
• Accurate genetic analysis is crucial for diagnosis and management.

Purpose of the Study:

• To analyze genetic mutations in the ATP7B gene associated with Wilson disease.
• To establish methods for prenatal and presymptomatic diagnosis of Wilson disease.

Main Methods:

• Sanger sequencing of the ATP7B gene was performed on 35 pedigrees.
• Polymerase chain reaction (PCR) was used to amplify exons and exon-intron boundaries.
• Prenatal diagnosis utilized chorionic villus sampling after parental genotype determination.

Main Results:

• A high mutation detection rate of 92.9% was achieved.
• 24 distinct mutations were identified, including 7 novel mutations.
• Common mutations included R778L (45.7%), A874V (7.1%), and P992L (7.1%).
• Two presymptomatic patients were identified and initiated treatment.
• Prenatal diagnosis confirmed three healthy fetuses and one carrier.

Conclusions:

• The R778L mutation is the most prevalent in the studied population.
• Seven novel ATP7B gene mutations were identified.
• Genetic counseling, prenatal, and presymptomatic diagnosis are recommended for Wilson disease pedigrees using Sanger sequencing and haplotype analysis.