The Clinical, Imaging Features And Genetic Research On A Genealogy Of Pelizaeus-merzbacher Disease

Objective:We summarize the clinical, imaging features of a Pelizaeus-Merzbacher disease(PMD) genealogy, by doing molecular genetics research to clarify the causes, provide accurate genetic counseling and prenatal diagnosis for other members of the family.Methods:We collected the clinical materials of the proband and his relatives who were diagnosed at the first hospital of Jilin University in September2014. The peripheral blood of the patient and his relatives were detected by multiplex ligation-dependent probe amplification(MLPA) to identify mutations of proteolipid protein l(PLP1). Then the relationship between phenotype and gene type would be further analyzed.Results:1. Clinical characteristics:The 37-year-old male was born after an uncomplicated full termpregnancy, and grew slowly from childhood. He was noted to havehorizontal nystagmus at about 1 month old. Around 2~3 years old,the patient was able to sit and walk with supporting. Since then hepresented regression of motor functions. The ability of walking was lost at 4~5 years old. Afterwards his increased muscle tone was revealed with positive Babinski reflexes, and positive ankle clonus. At 8 years old he developed severe spasticity, contractures in lowerlimbs and muscle wasting of the whole body. He could raise his upper limbs but with ataxia.He could not speak clearly. Fortunately, his cognitive impairment was not obvious. Similar clinical symptoms were found in six male members of his family, who spread out over five generations and three of them were died.2. Accessory examination:Magnetic resonance imaging(MRI) showed hyperintensity of the cerebral white matter on T1-weighted images, the ventricular system widened, sulci widened and deepened, Bilateral frontal subarachnoid space widened, cerebellar sulci widened and increased.3. Genetic testing results:The patient was diagnosed with the whole gene duplication mutation of PLP1 and both his mother and cousin were diagnosed as carriers of PLP1 gene duplication mutation. Combined with the clinical, imaging features and genetic research, he was diagnosed as PMD. Although the other patients did not detect the gene, based of the similar time of onset and clinical features, we considered they also suffered from the disease of PMD.Conclusions:1. The common clinical manifestations of the genealogy were horizontal nystagmus, growth retardation, muscle tension changing,contractures in lower limbs, which matched the PMD clinical diagnostic criteria.2. Genetic testing proved the patient was the duplication mutation of PLP1. According to genomic mutation analysis, PLP1 duplication was the most common mutation. His mother was the carrier of PLP1 gene duplication mutation.3. These findings provided accurate genetic counseling for other members of the family.