Feasibility of RNA studies on illegitimate transcription for molecular characterization of splicing mutations in the ATP7B gene: a case report.
Approximately 520 Wilson disease-causing mutations in the ATP7B gene have been described to date. In this study we report DNA and RNA analyses carried out for molecular characterization of a consensus sequence splicing mutation found in homozygosity in a Swiss Wilson disease patient. RNA analysis of 1946 +6 T→C in both the peripheral lymphoblasts and liver resulted in the production in the propositus of only an alternative transcript lacking exons 6, 7, and 8 resulting most likely in alterations of cell biochemistry and disease. The patient presents an early form of severe hepatic disease characterized by hepatosplenomegaly, reduced hepatic function, anemia and thrombocytopenia indicating that 1946 +6 T→C is a severe mutation. Since identical results were obtained from both peripheral lymphoblasts and liver they also suggest that RNA studies of illegitimate transcripts can be safely used for molecular characterization of ATP7B splicing mutations, thus improving genetic counseling and diagnosis of Wilson disease. Moreover these studies, contribute to reveal the exact molecular mechanisms producing Wilson disease.
Dipartimento di Scienze Biomediche e Biotecnologie, USC, Cagliari, Italy.
Antonietta
A
Zappu
Maria Barbara
MB
Lepori
Simona
S
Incollu
Valentina
V
Dessì
Maria Cristina
MC
Noli
Eva
E
Mameli
Luisa
L
Bonafé
Nuria
N
Garcia Dépraz
Stefano
S
De Virgiliis
Antonio
A
Cao
Georgios
G
Loudianos
D000251:Adenosine Triphosphatases / Q000235:genetics*; D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002648:Child; D016384:Consensus Sequence; D000073840:Copper-Transporting ATPases; D005260:Female; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics; D006720:Homozygote; D006801:Humans; D025202:Molecular Diagnostic Techniques; D017354:Point Mutation; D020033:Protein Isoforms / Q000235:genetics; D022821:RNA Splice Sites / Q000235:genetics; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic
D027682:Cation Transport Proteins; D020033:Protein Isoforms; D022821:RNA Splice Sites; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases