Diverse PAH transcripts in lymphocytes of PKU patients with putative nonsense (G272X, Y356X) and missense (P281L, R408Q) mutations

FEBS Letters

Eiken, Hans Geir¹  Knappskog, Per M¹  Ellingsen, Ståle¹  Apold, Jaran¹ 

[1] Department of Medical Genetics, Haukeland Hospital, University of Bergen, N-5021 Bergen, Norway

关键词: Phenylketonuria mutation;    Phenylalanine hydroxylase;    RNA splicing;   

DOI  :  10.1016/S0014-5793(99)01095-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The majority of mutations in the human phenylalanine hydroxylase (PAH) gene that lead to the recessive disease phenylketonuria (PKU) are believed to affect the activity or stability of the PAH enzyme. In this study we have performed in vivo analyses of lymphocyte PAH mRNA from PKU patients homozygous for the PKU missense mutations P281L and R408Q as well as the nonsense mutations G272X and Y356X. The mutations G272X, P281L and R408Q, which are located outside the consensus splice site sequence, result in transcripts with one or more exons skipped in addition to full-length transcripts. The mutation Y356X results in transcripts with one or more exons skipped, but no full-length transcripts. Our findings question the value of functional and structural predictions of mutations at the protein level without analyses of the corresponding transcript.

【 授权许可】

Unknown