Gene mutations and prenatal diagnosis in six pedigrees with Pelizaeus-Merzbacher disease
10.3760/cma.j.issn.1007-9408.2012.10.007
- VernacularTitle:六个佩梅病家系的蛋白脂蛋白1基因突变分析与产前诊断
- Author:
Mangmang GUO
;
Ye WU
;
Huixia YANG
;
Dongxiao LI
;
Haijuan ZHAO
;
Junya CHEN
;
Yu SUN
;
Xiru WU
;
Yuwu JIANG
;
Jingmin WANG
- Publication Type:Journal Article
- Keywords:
Pelizaeus-Merzbacher disease;
Proteolipid protein 1;
Pedigree;
Mutation;
Prenatal diagnosis
- From:
Chinese Journal of Perinatal Medicine
2012;15(10):599-604
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate proteolipid protein 1 (PLP1) mutations in six pedigrees with Pelizaeus-Merzbacher disease (PMD),and to provide prenatal consulting and prenatal diagnosis.Methods Subjects were six probands with PMD admitted in Department of Pediatrics,Peking University First Hospital from July 2006 to November 2011 and their family members.Genomic DNA sarnples were extracted from peripheral bloods of probands and their family members.Multiplex ligation-dependent probe amplification (MLPA) technique was used to detect PLP1 duplication mutation.Direct DNA sequencing was used to detect point mutation.Genetic diagnosis were based on PLP1 mutation genotype from probands.Prenatal diagnosis of nine fetuses were performed from seven PLP1 mutation female carriers by fetuses' DNA extracted from amniocytes or villus cells.Results PLP1 duplications were found in probands 1-4 (P1-4) whose mothers and the aunt of proband 1 (P1) were PLP1 duplications carriers.The two cases of point mutation,c.96C＞G(p.F32L) and c.623G＞T (p.G208V),were found in proband 5 (P5) and proband 6 (P6).Hcterozygous changes of the same mutations were found in P5' and P6' mothers with normal phenotypes.Seven female PLP1 mutation carriers were pregnant again.Prenatal diagnosis of PLP1 for nine fetuses presented one PLP1 duplication,one point mutation,one PLP1 duplication carrier,and six wildtypes.A segmental crossing over of X chromosome was detected in one male fetus of PLP1 wildtype.Conclusions PLP1 mutation analysis could help to diagnose PMD pedigree and to identify female PLP1 mutation carrier in the family.The following prenatal diagnosis and proper genetic counseling are very important to prevent PMD child from being delivered.
