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 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.
Bashyam
Murali D
MD
Laboratory of Molecular Oncology, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India. bashyam@cdfd.org.in
Chaudhary
Ajay K
AK
Reddy
E Chandrakanth
EC
Devi
A Radha Rama
AR
Savithri
G R
GR
Ratheesh
R
R
Bashyam
Leena
L
Mahesh
E
E
Sen
Dity
D
Puri
Ratna
R
Verma
Ishwar C
IC
Verma
Inder C
IC
Nampoothiri
Sheela
S
Vaidyanathan
Sunitha
S
Chandrashekar
Mataguru D
MD
Kantheti
Prameela
P
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
D022821:RNA Splice Sites; D010651:Phenylalanine Hydroxylase