4.7 Article

Mutational and phenotypic spectrum of phenylalanine hydroxylase deficiency in Zhejiang Province, China

Journal

SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-35373-9

Keywords

-

Funding

  1. National Key R&D Program of China [2017YFC1001703]
  2. key Medicine and Health Project of Zhejiang Province [WKJ-ZJ-1704]
  3. Zhejiang Provincial Program for the Cultivation of High level Innovative Health talents
  4. National Natural Science Foundation of China [81741090]

Ask authors/readers for more resources

Phenylalanine hydroxylase deficiency (PAHD), one of the genetic disorders resulting in hyperphenylalaninemia, has a complex phenotype with many variants and genotypes among different populations. Here, we describe the mutational and phenotypic spectrum of PAHD in a cohort of 420 patients from neonatal screening between 1999 and 2016. The observed phenotypes comprised 43.57% classic phenylketonuria, 33.10% mild PKU, and 23.33% mild hyperphenylalaninemia, with an overall PAHD incidence of 1 in 20,445. Genetic testing was performed for 209 patients and 72 variants including seven novel variants were identified. These included two synonymous and five pathogenic nonsynonymous variants (p.536*, p.T1861, p.L255W, p.F302V and p.R413H). The most common variant among all patients was p.R2430, followed by p.R241C, p.Y204C, p.R111* and c.442-1G > A. Variants p.R53H and p.F3921 occurred only in MHP with 19.3% and 8.0% of the observed alleles respectively. The genotypes p.[R241C];[R243Q], p.[R243Q];[R243Q], and p.[Y204C];[R243Q] were abundant across all PAHD patients. The distributions of the null allele and the three defined genotypes, null/null, null/missense, and missense/missense, were significantly different between the cPKU and mPKU patients. However, no significant differences were found between mPKU and MHP patients, indicating that other modifier factors influence the phenotypic outcome in these patients. The data presented here will provide a valuable tool for improved genetic counseling and management of future cases of PAHD in China.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available