Feasibility of RNA studies on illegitimate transcription for molecular characterization of splicing mutations in the ATP7B gene: A case report

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• 作者：Antonietta Zappu^a ; Maria Barbara Lepori^a ; Simona Incollu^a ; Valentina Dessì ; ^a ; Maria Cristina Noli^a ; Eva Mameli^a ; Luisa Bonaf&eacute ; ^b ; Nuria Garcia D&eacute ; praz^b ; Stefano De Virgiliis^c ; Antonio Cao^d ; Georgios Loudianos^e ; ^{gloudian@yahoo.com} ; ^{gloudian@mcweb.unica.it}
• 关键词：ATP7B ; Wilson disease ; Molecular diagnosis ; DNA ; RNA ; Illegitimate transcript
• 刊名：Molecular and Cellular Probes
• 出版年：2012
• 出版时间：April, 2012
• 年：2012
• 卷：26
• 期：2
• 页码：63-65
• 全文大小：258 K

文摘

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¡úC 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¡úC 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.