The Analysis Of Proteolipid Protein1Gene Mutation In A Case Of Pelizaeus-merzbacher Disease (PMD) Family Line

Objective:Pelizaeus-Merzbacher disease (PMD) is a rare x-linked recessive genetic diffuse brain white matter myelination barrier disease, In1885, Germany Pelizaeus F. initial described the clinical manifestations of this disease, In1910,Germany Merzbacher L found the characteristics which is x-linked recessive genetic, and there was dysmyelinating in white matter by microscope, PMD is one of the proteolipid protein1(PLP1) related genetic myelination obstacles spectrum of disease, In demyelinated diseases, PMD about6.6%. The symptoms including nystagmus, limbs paralysis, ataxia, motor delays, etc. The exact mechanism has not been elucidated. This study aims to collect and analysis the clinical features in a PMD children’s family line, and the mutations of PLP1gene. This study preliminary discuss the relationship between genotype and phenotype, and provide the accurate genetic consultation to PMD children’s family, offer exact experiment basis to prenatal diagnosis.Methods:Collect the proband and his family member’s clinical data. Detect the PLP1gene mutations by using the multiplex ligation-dependent probe amplification (MLPA) to determine the types of genetic mutations is not duplication, and all7exons and exon-intron boundaries of PLP1gene were amplified by polymerase chain reaction(PCR). Detect the PLP1gene mutations and confirm where gene point mutants by direct DNA sequencing and DNA restriction enzyme digestion, and analysis the relationship between genotype and phenotype.Results:(1) Clinical outcomes:Infant is a boy, born in August2004, with weak, horizontal nystagmus, motor delays, but there is still slow progress. There are horizontal nystagmus lower-limb muscle hypertonia; lower-limb knee jerk reflex led; bilateral positive Babinski sign, especially right; bilateral strephenopodia. MRI shows:neonatal white matter myelination. There are13male patients in4-generation of same family line. Infant’s brother died in8with similar pathography.(2) Gene mutation analysis:In this study, the PLP1genetic testing results show that the point mutations occurred in child’s PLP1gene. One heterozygous mutations of PLP1were identified c.96C>G (p.F32L) in exon2from proband.The heterozygous change c.96C>G (p.F32L) in exon2was found in the proband’s mother、grandmother and grand grandmother with normal phenotype,and the proband’s father、two aunts with normal genotype and phenotype.Conclusions:1. The case suffer from horizontal nystagmus、growth retardation、Muscle tension change、head MRI characteristic changes, which meets the PMD clinical diagnostic criteria.2. The PLP1gene mutation analysis of this case shows one nucleotide alteration [c.96C＞G (p.F32L)], and the change was found in the proband’s mother、grandmother and grand grandmother with normal phenotype, and the proband’s father、two aunts with normal genotype and phenotype. This change is a new mutation which is not reported. This research expand the PLP1gene mutation profile. c.96C＞G (p.F32L) likely to be a Chinese PMD children’s hot-spot mutation.3. The PLP1gene point mutation found in this case is able to perform exact genetic counseling and prenatal diagnosis for the proband and his family...