title: Phenylalanine hydroxylase gene mutations in phenylketonuria patients from India: identification of novel mutations that affect PAH RNA.
abstract: 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.
authors.affiliation: Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India. bashyam@cdfd.org.in
authors.forename: Murali D
authors.initials: MD
authors.lastname: Bashyam
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Chaudhary
authors.forename: E Chandrakanth
authors.initials: EC
authors.lastname: Reddy
authors.forename: A Radha Rama
authors.initials: AR
authors.lastname: Devi
authors.forename: G R
authors.initials: GR
authors.lastname: Savithri
authors.forename: R
authors.initials: R
authors.lastname: Ratheesh
authors.forename: Leena
authors.initials: L
authors.lastname: Bashyam
authors.forename: E
authors.initials: E
authors.lastname: Mahesh
authors.forename: Dity
authors.initials: D
authors.lastname: Sen
authors.forename: Ratna
authors.initials: R
authors.lastname: Puri
authors.forename: Ishwar C
authors.initials: IC
authors.lastname: Verma
authors.forename: Inder C
authors.initials: IC
authors.lastname: Verma
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Sunitha
authors.initials: S
authors.lastname: Vaidyanathan
authors.forename: Mataguru D
authors.initials: MD
authors.lastname: Chandrashekar
authors.forename: Prameela
authors.initials: P
authors.lastname: Kantheti
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000201:enzymology / Q000235:genetics*; D022821:RNA Splice Sites; D017384:Sequence Deletion
chemical_list: D022821:RNA Splice Sites; D010651:Phenylalanine Hydroxylase