Abstract:

A patient with an unusually mild form of Pelizaeus-Merzbacher disease was studied. Clinically, mild developmental delay with acquisition of assisted walking at 16months and mild spastic tetraplegia were evident, but no nystagmus, cerebellar, or extra-pyramidal signs were present. PLP1 mutation analysis revealed a nucleotide substitution adjacent to the acceptor site of intron 3, NM_000533.4:c.454-9T>G. Expression analysis using the patient's leukocytes demonstrated an additional abnormal transcript including the last 118bp of intron 3. In silico prediction analysis suggested the reduction of wild-type acceptor activity, which presumably evokes the cryptic splicing variant. Putative cryptic transcript results in premature termination, which may explain the mild clinical phenotype observed in this patient.

日本語要旨:

軽症型のPelizaeus-Merzbacher病症例を報告した。PLP1遺伝子解析にてイントロン３のc.454-9T>G変異を同定した。この変異によってスプライシング異常を引き起すこと考えられ、これらの以上スプライシング産物は全て早期終止コドンを持つと予想されることから、本患者の臨床症状が軽症型であること考えられた。