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MOLECULAR ANALYSIS FOR SIBLING CASES OF WILSON DISEASE WITH DIFFERENT PHENOTYPE

Takeshita Y¹⁾, Shimizu N¹⁾, Hemmi H²⁾, Shimatake H²⁾, Aoki T¹⁾

¹⁾ 2nd Department of Pediatrics, Toho University School of Medicine, Ohashi Hospital

²⁾ Department of Molecular Biology, Toho University School of Medicine

Introduction: Wilson disease is an autosomal recessive disorder caused by defective function of copper transporting P-type ATPase. This disease is clinically characterized by hepatic and neurological manifestations related to the accumulation of copper in the liver and the brain. Usually, sibling cases in this disease appeared same clinical coarse and same onset age. We diagnosed 2 families (3 and 2 sibs) with different phenotype and different onset age, and performed molecular analysis for them to investigate phenotype-genotype correlation in this disease.

Family 1: A forty-seven year old female, she manifested hepatic phenotype after deliver at 35 years old. She had two younger brothers who were neurologic type of Wilson disease, and onset ages were 15 and 16 years old.

Family 2: A thirty-five years old female, she was hepatic type of Wilson disease. She had found out familial screening. Because her younger brother was diagnosed as neurologic type of this disease at 32 years old.

Gene analysis: Genomic DNAs were isolated from peripheral blood from these patients. We amplified each exons of A TP7B gene, then analyzed them by direct sequencing method.

Results and Discussion: Both of two families showed compound heterozygous mutations. Family 1 was Arg778Leu in exon 8 and Arg919 Gly in exon 12. Mutation of one allele of family 2 was 2659 del C in exon 11 and another one was still unknown. The development of different phenotype in one family may be related with heterozygous gene mutations.