|Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease|
|Wang Jing-min1; Wu Ye1; Wang Hui-fang2; Deng Yan-hua2; Yang Yan-ling1; Qin Jiong1; Li Xin-yi2; Wu Xi-ru1; Jiang Yu-wu1|
|关键词||Pelizaeus-Merzbacher disease proteolipid protein 1 gene multiplex ligation-dependent probe amplification mutation|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||DEPENDENT PROBE AMPLIFICATION ; SPASTIC PARAPLEGIA TYPE-2 ; CENTRAL-NERVOUS-SYSTEM ; PROTEIN GENE ; MYELIN ; DUPLICATIONS ; PATHOGENESIS ; DISORDERS ; PCR|
Background Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive disorder with symptoms including nystagmus, impaired motor development, ataxia, and progressive spasticity. The proteolipid protein 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 blood samples. Gene dosage was determined using the multiplex ligation-dependent probe amplification (MLPA). All 7 exons and exon-intron boundaries of the PLP1 gene were amplified and analyzed using direct DNA sequencing.
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 PLP1 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.
|项目编号||2007CB5119004 ; D43 TW06176|
|资助机构||Science and Technology Ministry of China ; Scientific Research Foundation for Returned Overseas Chinese Scholars of State Education Ministry of China ; NIH/FIC|
|作者单位||1.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China|
2.Shanxi Med Univ, Dept Neurol, Hosp 1, Taiyuan 030001, Shanxi, Peoples R China
|Wang Jing-min,Wu Ye,Wang Hui-fang,et al. Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease[J]. CHINESE MEDICAL JOURNAL,2008,121(17):1638-1642.|
|APA||Wang Jing-min.,Wu Ye.,Wang Hui-fang.,Deng Yan-hua.,Yang Yan-ling.,...&Jiang Yu-wu.(2008).Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease.CHINESE MEDICAL JOURNAL,121(17),1638-1642.|
|MLA||Wang Jing-min,et al."Proteolipid protein 1 gene mutation in nine patients with Pelizaeus-Merzbacher disease".CHINESE MEDICAL JOURNAL 121.17(2008):1638-1642.|