Y S Yan1, F X Yao2, S J Hao, C Zhang, X Chen, X Feng, T Yang, S Z Huang. 1. Gansu Province Maternal and Child Health Care Hospital, Gansu Province Medical Genetics Center, Gansu Province Prenatal Diagnosis Center, Lanzhou 730050, China. 2. 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.
Abstract
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.
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 PKUpatients 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 PKUpatients. It's important to detect the large del/dup mutation, and there are different hotspot mutation genotypes in Chinese patients.