Proteolipidprotein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease  

作　　者：WANG Jing-min WU Ye WANG Hui-fang DENG Yan-hua YANG Yan-ling QIN Jiong LI Xin-yi WU Xi-ru JIANG Yu-wu 

机构地区：[1]Department of Pediatrics, Peking University First Hospital, Beijing 100034, China [2]Department of Neurology, First Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030001, China

出　　处：《Chinese Medical Journal》2008年第17期1638-1642,共5页中华医学杂志（英文版）

摘　　要：Background Pelizaeus-Merzbacher disease （PMD） is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipidprotein 1 （PLP1） gene is the only pathogenic gene of PMD. Duplication of the PLP1 gene is the most frequent gene defect, accounting for 50%-70% of PMD cases, whereas point mutations in the coding sequence or the splice sites account for 10%-25% of PMD cases. This study aimed to identify PLP1 mutations in nine unrelated Chinese patients （P1-9） with PMD, and 14 subjects from the family of patient 2 were also described. Methods Genomic DNA was extracted from peripheral multiplex ligation-dependent probe amplification （MLPA）. AI amplified and analyzed using direct DNA sequencing. blood samples. Gene dosage was determined using the 7 exons and exon-intron boundaries of the PLP1 gene were Results Of these nine patients, there were four transitional, four classical, and one connatal PMD according to their clinical and radiological presentations. PLP1 duplications were identified in patients 1-7 with PMD. Their mothers were PLPI duplications carriers as well. Both duplication carriers and normal genotypes of PLP1 were identified in the family members of patient 2. A c.517C〉T （p. P173S） hemizygous missense mutation in exon 4 was found in patient 8 with PMD, and his mother was shown to be a heterozygote of this mutation. Conclusions We identified seven genomic duplications and one missense mutation （p. P173S） of the PLP1 gene in eight Chinese patients with PMD. This is the report about PLP1 mutations in PMD patients from the mainland of China.Background Pelizaeus-Merzbacher disease （PMD） is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipidprotein 1 （PLP1） gene is the only pathogenic gene of PMD. Duplication of the PLP1 gene is the most frequent gene defect, accounting for 50%-70% of PMD cases, whereas point mutations in the coding sequence or the splice sites account for 10%-25% of PMD cases. This study aimed to identify PLP1 mutations in nine unrelated Chinese patients （P1-9） with PMD, and 14 subjects from the family of patient 2 were also described. Methods Genomic DNA was extracted from peripheral multiplex ligation-dependent probe amplification （MLPA）. AI amplified and analyzed using direct DNA sequencing. blood samples. Gene dosage was determined using the 7 exons and exon-intron boundaries of the PLP1 gene were Results Of these nine patients, there were four transitional, four classical, and one connatal PMD according to their clinical and radiological presentations. PLP1 duplications were identified in patients 1-7 with PMD. Their mothers were PLPI duplications carriers as well. Both duplication carriers and normal genotypes of PLP1 were identified in the family members of patient 2. A c.517C〉T （p. P173S） hemizygous missense mutation in exon 4 was found in patient 8 with PMD, and his mother was shown to be a heterozygote of this mutation. Conclusions We identified seven genomic duplications and one missense mutation （p. P173S） of the PLP1 gene in eight Chinese patients with PMD. This is the report about PLP1 mutations in PMD patients from the mainland of China.

关 键 词：Pelizaeus-Merzbacher disease proteolipid protein 1 gene multiplex ligation-dependent probeamplification MUTATION 

分 类 号：R596[医药卫生—内科学]