33 Cases Peja Mei Disease Plp1 Mutation Analysis And 5 Cases Of Prenatal Diagnosis

Pelizaeus-Merzbacher disease(PMD) is a rare X-linked recessive leukoencephalopathy characterized by nystagmus, ataxia and cognitive impairment. In the USA, the prevalence of PMD is estimated to be about1/300,000to1/500,000, and in the Germany is0.13of every100,000live-born infants. The main cause of PMD is alterations of the proteolipid protein1(PLP1)gene. The PLP1gene is located in Xq22.2. which encodes PLP1protein. Duplication of the PLP1gene is the most frequent gene defect accounting for50-70%of PMD cases.Objective:Analyze and identify the mutation types and genetics characteristics of PLP1Gene in33children with PMD, investigate the relationship between the genotype and the phenotype and provide assistance for diagnosis, genetic counseling and prenatal diagnosis. Meanwhile, make prenatal diagnosis for the families of gene diagnosis patients(5cases).Methods:Genomic DNA from33children with PMD and genomic DNA extracted from amniotic fluid of probands’ mothers during18～22gestigation weeks, and used multiplex ligation-dependent probe amplification(MLPA) techniques and polymerase chain reaction (PCR) detected PLP1gene duplication,deletion and point mutation.Results:1. In33patients, they were diagnosed PMD with nystagmus, impaired motor development, ataxia, and progressive movement disorder of extremities were slectived and all of them were male. Cranial MRI of the patients demonstrated retardation of myelin development. According to the clinical manifestation, the patients were diagnosed congenital type (3children), intermediate type(11children) and classic type(19children); make prenatal diagnosis for the families of gene diagnosis patients during18-22gestigation weeks.2.29patients presented PLP1gene mutation (87.88%,29/33).whose mothers were all mutation carriers.23children of them were duplication mutation and account for79.31%(23/29),17of which were classic type,2of which were congenital type and the other4were intermediate type;6children of them were point mutation and account for20.69%(6/29),2of which were classic type,2of which were congenital type and the other2were intermediatetype. 3. According to the results of prenatal diagnosis, one girl and two boy were normal genotype, one girl was duplication mutation carrier of PLP1gene and one boy was with PLP1gene duplication mutation.Conclusions:1. The patients were selected for the characteristic change with PMD, in line with the clinical diagnosis of PMD.2.33cases with PMD PLP1gene mutation were found29cases, Which duplication mutation account81.25%and point mutation account18.75%. which c.623G> T (p.G208V), C.709T> G (p.F237V), c.353C> G (p. T118R)were new mutations, expanding the PLPl gene mutation spectrum.3. The relationship between genotype and phenotype:PLP1gene mutations are common as duplication, and the majority of cases are type of classical.4. Precise genetic counseling and prenatal diagnosis can be provided for probands with PMD and their families. We made prenatal diagnosis for the PMD carriers’mothers successfully.5. It is the first time to diagnose PMD by genetic detection in China.