Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)
Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)
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DOI：
10.1212/01.wnl.0000138429.11433.0d
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发表时间：
2004-09-28
期刊：
影响因子：
9.9
通讯作者：
Minetti, C
中科院分区：
文献类型：
--
作者：
Bruno, C;van Diggelen, OP;Minetti, C
背景：糖原储存病IV型（GSD-IV）是一种临床异质性常染色体隐性遗传病，由于糖原分支酶（GBE）缺乏，导致支链淀粉样多糖积累。典型的表现是儿童期肝脏疾病，发展为致命性肝硬化。GSD-IV的神经肌肉形式在发病（围产期、先天性、青少年或成人）和严重程度上各不相同。目的：鉴定不同神经肌肉型GSD-IV的分子基础，并建立可能的基因型/表型相关性。方法：8例GBE缺乏症患者有不同的神经肌肉表现：3例有胎儿动功能变形序列（FADS）， 3例有先天性肌病，1例有青少年肌病，1例有肌病和肝脏合并特征。在所有患者中，在RNA和基因组水平上对GBE基因的启动子和整个编码区进行测序。结果：鉴定出9个新的突变，包括无义突变、错义突变、缺失突变、插入突变和剪接突变。3例FADS为纯合子，其余均为复合杂合子。结论：本研究扩大了GBE基因突变谱，证实了GSD-IV的神经肌肉表现具有临床和遗传异质性。
Background: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity. Objective: To identify the molecular bases of different neuromuscular forms of GSD-IV and to establish possible genotype/phenotype correlations. Methods: Eight patients with GBE deficiency had different neuromuscular presentations: three had fetal akinesia deformation sequence (FADS), three had congenital myopathy, one had juvenile myopathy, and one had combined myopathic and hepatic features. In all patients, the promoter and the entire coding region of the GBE gene at the RNA and genomic level were sequenced. Results: Nine novel mutations were identified, including nonsense, missense, deletion, insertion, and splice-junction mutations. The three cases with FADS were homozygous, whereas all other cases were compound heterozygotes. Conclusions: This study expands the spectrum of mutations in the GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically and genetically heterogeneous.