Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene
Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene
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DOI：
10.1002/ana.410440604
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发表时间：
1998-12-01
影响因子：
11.2
通讯作者：
Meiner, V
中科院分区：
文献类型：
--
作者：
Lossos, A;Meiner, Z;Meiner, V
成人多葡聚糖体病（APBD）是一种由糖原分支酶（GBE）缺乏引起的晚发性、缓慢进展的神经系统疾病，发生在德系犹太人亚组患者中。与APBD不同的是，IV型糖原储存病（GSD TV）是一种早期儿童疾病，主要表现为全身症状。最近，研究人员克隆了GEE cDNA，并在不同临床形式的GSD IV中发现了几种突变。为了研究GEE基因突变是否与APBD有关，我们研究了来自5个德系犹太人家族的7名患者。诊断是基于典型的临床和病理表现，并支持减少GEE活动。我们发现，所有5个家族的临床和生化APBD表型与Tyr(329)Ser突变共分离，而在140个对照中未检测到。由于该突变先前在非进展型GSD IV中被发现，并且在表达研究中显示导致显著的残余GEE活性，因此本研究结果解释了我们患者中APBD的晚发和缓慢进展过程。我们得出结论，APBD代表GSD IV的等位变异，但必须确定原发组织受累差异的原因。
Adult polyglucosan body disease (APBD) is a late-onset, slowly progressive disorder of the nervous system caused by glycogen branching enzyme (GBE) deficiency in a subgroup of patients of Ashkenazi Jewish origin. Similar biochemical finding is shared by glycogen storage disease type IV (GSD TV) that, in contrast to APBD, is an early childhood disorder with primarily systemic manifestations. Recently, the GEE cDNA was cloned and several mutations were characterized in different clinical forms of GSD IV. To examine whether mutations in the GEE gene account for APBD, we studied 7 patients from five Jewish families of Ashkenazi ancestry. The diagnosis was based on the typical clinical and pathological findings, and supported by reduced GEE activity. We found that the clinical and biochemical APBD phenotype in all five families cosegregated with the Tyr(329)Ser mutation, not detected in 140 controls. As this mutation was previously identified in a nonprogressive form of GSD IV and was shown in expression studies to result in a significant residual GEE activity, present findings explain the late onset and slowly progressive course of APBD in our patients. We conclude that APBD represents an allelic variant of GSD IV, but the reason for the difference in primary tissue involvement must be established.