[Analysis of large deletion of phenylalanine hydroxylase gene in Chinese patients with phenylketonuria].
OBJECTIVE
To analyze the types and distribution of large deletion of phenylalanine hydroxylase (PAH) gene in Chinese patients with phenylketonuria (PKU).


METHODS
On the basis of 953 PKU patients from Peking Union Medical College and Gansu Province Medical Genetics Center, which were detected by directed sequencing of PAH gene between 2006 and 2014. Multiplex ligation-dependent probe amplification (MLPA) of PAH gene was performed in 43 patients with one or two unknown genotypes. And the deletion breakpoints were characterized by Gap PCR-sequencing.


RESULTS
Twenty-four large deletion/duplication alleles were found in 22 patients, accounting for 51.1%(24/47)of the 47 unknown mutations of the 43 patients.There were 6 different large deletions, including Ex1del3758 (n=10), Ex4_5del (n=4), Ex4_7del (n=3), Ex1del5329ins56 (n=3), Ex3del6599ins8 (n=2), and Ex4del (n=1); and 1 duplication was found (Ex12dup, n=1). The most common large deletions in Chinese patients were Ex1del3758 (21.3%), Ex4_5del (8.5%), and Ex4_7del (6.4%).


CONCLUSIONS
Large deletion mutations of PAH gene are present in Chinese PKU patients. It's important to detect the large del/dup mutation, and there are different hotspot mutation genotypes in Chinese patients.
Gansu Province Maternal and Child Health Care Hospital, Gansu Province Medical Genetics Center, Gansu Province Prenatal Diagnosis Center, Lanzhou 730050, China.
Y S
YS
Yan
Center of Prenatal Diagnosis, Clinical Genetics Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
F X
FX
Yao
S J
SJ
Hao
C
C
Zhang
X
X
Chen
X
X
Feng
T
T
Yang
S Z
SZ
Huang
D000483:Alleles; D044466:Asian People / Q000235:genetics*; D005091:Exons; D005838:Genotype; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000208:ethnology / Q000235:genetics; D017384:Sequence Deletion
D010651:Phenylalanine Hydroxylase