Phenylketonuria mutations in Northern China

Area of Science:

• Genetics
• Molecular Biology
• Biochemistry

Background:

• Phenylketonuria (PKU) is a genetic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene.
• Understanding the specific mutation spectrum in different populations is crucial for genetic diagnosis and counseling.
• Previous studies have characterized PKU mutations globally, but data from Northern China remained limited.

Purpose of the Study:

• To comprehensively analyze the mutation spectrum of the PAH gene in patients with PKU from Northern China.
• To investigate the genotype-phenotype correlations in this patient cohort.
• To establish a foundation for a national PKU database in China.

Main Methods:

• Polymerase Chain Reaction/Single-Strand Conformation Polymorphism (PCR/SSCP) and DNA sequencing were employed.
• All exons of the PAH gene were analyzed in 185 unrelated PKU patients from Northern China.
• Mutation identification and frequency calculation were performed.

Main Results:

• A total of 70 distinct PAH gene mutations were identified in 349 out of 370 mutant alleles (94.3%).
• Novel mutations, including deletion, insertion, and frameshift types, were reported for the first time in Chinese PKU patients.
• Prevalent mutations (R243Q, EX6-96A>G, R111X, Y356X, R413P) accounted for a significant proportion of mutant alleles, with 15 novel mutations identified at low frequencies.

Conclusions:

• The PKU mutation spectrum in Chinese populations shares similarities with other Asian populations but differs markedly from European populations.
• Genotype-phenotype correlation analysis revealed that predicted residual activity generally aligns with in vivo phenotypes, though some inconsistencies were observed.
• This comprehensive mutation data is vital for developing a national database for genetic counseling and prognostic evaluation of PKU in China.