Phenylalanine hydroxylase gene mutations in phenylketonuria patients from India: Identification of novel mutations that affect PAH RNA

Analysis of seven Indian phenylketonuria families has revealed four novel mutations in the phenylalanine hydroxylase gene; two affected consensus splice sequence and the 3′ UTR, respectively, while the other two were single base insertion and deletion mutations, respectively. A novel 3′ splice site...

Full description

Saved in:
Bibliographic Details
Published in:Molecular genetics and metabolism 2010-05, Vol.100 (1), p.96-99
Main Authors: Bashyam, Murali D., Chaudhary, Ajay K., Reddy, E. Chandrakanth, Rama Devi, A. Radha, Savithri, G.R., Ratheesh, R., Bashyam, Leena, Mahesh, E., Sen, Dity, Puri, Ratna, Verma, Inder C., Nampoothiri, Sheela, Vaidyanathan, Sunitha, Chandrashekar, Mataguru D., Kantheti, Prameela
Format: Article
Language:English
Subjects:
Adolescent
Adult
Child
Child, Preschool
Conserved sequence
Female
Humans
Male
Mutation
Nonsense-mediated decay
Phenylalanine hydroxylase
Phenylalanine Hydroxylase - genetics
Phenylketonuria
Phenylketonurias - enzymology
Phenylketonurias - genetics
RNA Splice Sites
Sequence Deletion
Splicing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Analysis of seven Indian phenylketonuria families has revealed four novel mutations in the phenylalanine hydroxylase gene; two affected consensus splice sequence and the 3′ UTR, respectively, while the other two were single base insertion and deletion mutations, respectively. A novel 3′ splice site mutation c.168-2A>G resulted in the activation of a cryptic 3′ splice site that generated a premature termination codon leading to very low levels of the mutant transcript, probably due to activation of the nonsense-mediated decay (NMD) pathway. This is probably the first report of PKU caused by the activation of NMD.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2010.01.016