Pontocerebellar Hypoplasia Type 6: A British Case With PEHO-Like Features
Pontocerebellar Hypoplasia Type 6: A British Case With PEHO-Like Features
复制标题
DOI：
10.1002/ajmg.a.33531
复制
发表时间：
2010-08-01
影响因子：
2
通讯作者：
Brown, Garry
中科院分区：
文献类型：
--
作者：
Rankin, Julia;Brown, Ruth;Brown, Garry
常染色体隐性遗传性脑桥小脑发育不全 (PCH) 已确定为六种亚型，其中四种亚型（PCH1、PCH2、PCH4 和 PCH6）的遗传基础已知。 PCH6 与脑萎缩和肌肉中多种但可变的呼吸链缺陷有关，并且在一个近亲西班牙裔犹太家庭中已有报道。它是由编码线粒体精氨酸转移 RNA 合成酶的 RARS2 基因突变引起的。在这里，我们描述了一位由非近亲英国父母所生的女性患者。她在新生儿期出现呼吸频率增加、喂养不良以及血液和脑脊液乳酸水平短暂升高的症状。她随后表现出严重的发育迟缓和严重的小头畸形。手、足和面部水肿提示 PEHO 样病症（进行性脑病、水肿、高度节律失常和视神经萎缩），尽管不存在视神经萎缩和高度节律失常。 14 个月大时的头颅 MRI 显示全身性脑萎缩、脑桥变薄以及小脑半球严重萎缩和扁平。两次肌肉活检均正常，呼吸链研究也正常。尽管不存在呼吸链缺陷，但该表型被认为与 PCH6 一致，并且确实鉴定出了两种新的致病性 RARS2 突变。我们的报告是由于 RARS2 突变引起的 PCH6 的第二份报告，并表明呼吸链异常不是必然的，而 PEHO 的某些特征可能存在。 (C) 2010 Wiley-Liss, Inc.
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. (C) 2010 Wiley-Liss, Inc.