Liu Yi-Hui, Zhang Hai-Feng, Jin Jie-Yuan, Wei Yan-Qiu, Wang Chen-Yu, Fan Liang-Liang, Liu Lv
Department of Respiratory Medicine, Diagnosis and Treatment Center of Respiratory Disease, The Second Xiangya Hospital of Central South University, Changsha, China.
Department of Neurology, Affiliated Hospital of Yangzhou University, Yangzhou, China.
Front Aging Neurosci. 2021 Jun 29;13:671296. doi: 10.3389/fnagi.2021.671296. eCollection 2021.
Leukodystrophies are a heterogeneous group of inherited disorders with highly variable clinical manifestations and pathogenetic backgrounds. At present, variants in more than 20 genes have been described and may be responsible for different types of leukodystrophies. Members of the phospholipase D family of enzymes catalyze the hydrolysis of membrane phospholipids. Meanwhile, phospholipase D3 (PLD3) has also been found to exhibit single stranded DNA (ssDNA) acid 5' exonuclease activity. Variants in () may increase the risk of Alzheimer's disease and spinocerebellar ataxia, but this hypothesis has not been fully confirmed. In this study, we identified a novel homozygous mutation (NM_012268.3: c.186C>G/ p.Y62X) of in a consanguineous family with white matter lesions, hearing and vision loss, and kidney disease by whole exome sequencing. Real-time PCR revealed that the novel mutation may lead to non-sense-mediated messenger RNA (mRNA) decay. This may be the first case report on the homozygous mutation of PLD3 in patients worldwide. Our studies indicated that homozygous mutation of may result in a novel leukoencephalopathy syndrome with white matter lesions, hearing and vision loss, and kidney disease.
脑白质营养不良是一组具有高度可变临床表现和致病背景的遗传性疾病。目前，已描述了20多个基因的变异，这些变异可能导致不同类型的脑白质营养不良。磷脂酶D家族的酶成员催化膜磷脂的水解。同时，还发现磷脂酶D3（PLD3）具有单链DNA（ssDNA）5'核酸外切酶活性。（）中的变异可能会增加患阿尔茨海默病和脊髓小脑共济失调的风险，但这一假说尚未得到充分证实。在本研究中，我们通过全外显子组测序在一个患有白质病变、听力和视力丧失以及肾脏疾病的近亲家庭中鉴定出一种新的纯合突变（NM_012268.3：c.186C>G/p.Y62X）。实时PCR显示，这种新突变可能导致无义介导的信使RNA（mRNA）降解。这可能是全球首例关于PLD3纯合突变患者的病例报告。我们的研究表明，（）的纯合突变可能导致一种新的白质脑病综合征，伴有白质病变、听力和视力丧失以及肾脏疾病。
