Prenatal diagnosis and PAH gene mutations in 55 pedigrees with phenylketonuria
10.3760/cma.j.issn.1007-9408.2018.11.009
- VernacularTitle:55个苯丙酮尿症家系产前诊断与基因突变分析
- Author:
Chuan ZHANG
1
;
Shengju HAO
;
Xiaoli WANG
;
Huiling WANG
;
Qinghua ZHANG
;
Lei ZHENG
;
Qing LIU
;
Xiaojuan LIN
;
Bingbo ZHOU
;
Yousheng YAN
;
Yali LIU
Author Information
1. 甘肃省妇幼保健院甘肃省出生缺陷防控研究重点实验室
- Keywords:
Phenylketonurias;
Prenatal diagnosis;
Phenylalanine hydroxylase;
Genetic testing
- From:
Chinese Journal of Perinatal Medicine
2018;21(11):764-768
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate phenylalanine hydroxylase ( PA H ) gene mutations and to perform prenatal diagnosis in 55 pedigrees with classical phenylketonuria (PKU). Methods Subjects of this study were 55 probands diagnosed with PKU in the Gansu Provincial Maternal and Child Health Care Hospital from 2013 to 2017 and their pedigrees. Sanger sequencing/Multiplex ligation-dependent probe amplification (MLPA) was used to investigate PA H gene mutations in these probands and their parents. Sanger sequencing/MLPA, linkage analysis of three common short tandem repeats (STR) including PAH-26, PAH-STR and PAH-32 in the PA H gene and paternity testing were used in combination for prenatal diagnosis of 60 fetuses in the 55 pedigrees. Results Among the 110 alleles in the 55 probands, 108 mutant alleles (98.2%) were found by Sanger sequencing. The 108 mutant alleles located in 38 regions resulting in 22 missense mutations, nine splice site mutations, five nonsense mutations and two microdeletion. The most common mutations were c.728G>A (22.2%, 24/108), c.442-1G>A (5.6%, 6/108), c.611A>G (5.6%, 6/108), c.764T>C (5.6%, 6/108), c.1068C>A (5.6%, 6/108) and c.331C>T (4.6%, 5/108). Loss of heterozygosity in 4-5 and 4-7 exons were detected by MLPA in two probands, in which only one mutation was unidentified. Prenatal diagnosis for the 60 fetuses were successfully performed. Among them, 17 fetuses (28.3%) were affected, 29 fetuses (48.3%) were heterozygous carriers and fetuses 14(23.4%) were unaffected ones. Conclusions Combination of Sanger sequencing/MLPA, linkage analysis and paternity testing could provide accurate prenatal diagnosis in pedigrees with PKU.
