Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient with spastic paraplegia derived from a single-nucleotide deletion in PLP1
書誌事項
- 公開日
- 2019-04-19
- 資源種別
- journal article
- 権利情報
-
- http://www.springer.com/tdm
- DOI
-
- 10.1038/s10038-019-0600-x
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
Pelizaeus-Merzbacher disease (PMD) is an X-linked recessive disorder caused by abnormalities in the gene PLP1. Most females harboring heterozygous PLP1 abnormalities are basically asymptomatic. However, as a result of abnormal patterns of X-chromosome inactivation, it is possible for some female carriers to be symptomatic. Whole-exome sequencing of a female patient with unknown spastic paraplegia was performed to obtain a molecular diagnosis. As a result, a de novo heterozygous single-nucleotide deletion in PLP1 [NM_000533.5(PLP1_v001):c.783del; p.Thr262Leufs*20] was identified. RNA sequencing was performed in a patient-derived lymphoblastoid cell line, confirming mono-allelic expression of the mutated allele and abnormal inactivation of the wild-type allele. The patient-derived lymphoblastoid cell line was then treated with VX680 or 5azadC, which resulted in restored expression of the wild-type allele. These two agents thus have the potential to reverse inappropriately-skewed inactivation of the X-chromosome.
収録刊行物
-
- Journal of Human Genetics
-
Journal of Human Genetics 64 (7), 665-671, 2019-04-19
Springer Science and Business Media LLC
