Peninsula Clinical Genetics Service, Exeter, UK.
Am J Med Genet A. 2010 Aug;152A(8):2079-84. doi: 10.1002/ajmg.a.33531.
Six subtypes of autosomal recessive pontocerebellar hypoplasia (PCH) have been identified and the genetic basis of four of these (PCH1, PCH2, PCH4, and PCH6) is known. PCH6 is associated with cerebral atrophy and multiple but variable respiratory chain defects in muscle and has been reported in one consanguineous Sephardic Jewish family. It is caused by mutations in the RARS2 gene which encodes mitochondrial arginine-transfer RNA synthetase. Here we describe a female patient born to nonconsanguineous British parents. She presented in the neonatal period with increased respiratory rate, poor feeding and transiently elevated blood and CSF lactate levels. She went on to manifest profound developmental delay and severe microcephaly. Edema of the hands, feet, and face were suggestive of a PEHO-like condition (progressive encephalopathy, edema, hypsarrhythmia and optic atrophy), although optic atrophy and hypsarrhythmia were absent. Cranial MRI at age 14 months showed generalized cerebral atrophy, thinning of the pons and gross atrophy and flattening of the cerebellar hemispheres. Muscle biopsies on two occasions were normal with normal respiratory chain studies. Despite the absence of respiratory chain defects, the phenotype was felt to be consistent with PCH6 and indeed two novel pathogenic RARS2 mutations were identified. Ours is the second report of PCH6 due to RARS2 mutations and demonstrates that respiratory chain abnormalities are not obligatory, whereas some features of PEHO might be present.
已经确定了六种常染色体隐性小脑桥脑萎缩（PCH）亚型，其中四种（PCH1、PCH2、PCH4 和 PCH6）的遗传基础已为人所知。PCH6 与脑萎缩和肌肉中多种但可变的呼吸链缺陷有关，已在一个近亲 Sephardic 犹太家庭中报道过。它是由线粒体精氨酸转移 RNA 合成酶基因（RARS2）的突变引起的。在这里，我们描述了一位出生于非近亲英国父母的女性患者。她在新生儿期表现为呼吸频率增加、喂养不良和短暂性血和 CSF 乳酸水平升高。随后，她表现出严重的发育迟缓及严重的小头畸形。手部、足部和面部的水肿提示存在 PEHO 样疾病（进行性脑病、水肿、高振幅脑电活动和视神经萎缩），尽管不存在视神经萎缩和高振幅脑电活动。在 14 个月大时进行的颅脑 MRI 显示大脑普遍萎缩、脑桥变薄以及小脑半球明显萎缩和平坦化。两次肌肉活检均正常，呼吸链研究正常。尽管没有呼吸链缺陷，但表型被认为与 PCH6 一致，事实上，还发现了两种新的致病性 RARS2 突变。我们的报告是由于 RARS2 突变导致的 PCH6 的第二个案例，证明了呼吸链异常并非必需的，而 PEHO 的一些特征可能存在。
