Analysis of GBE1 mutations via protein expression studies in glycogen storage disease type IV: A report on a non-progressive form with a literature review.
Analysis of GBE1 mutations via protein expression studies in glycogen storage disease type IV: A report on a non-progressive form with a literature review.
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DOI：
10.1016/j.ymgmr.2018.09.001
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发表时间：
2018-12
影响因子：
1.9
通讯作者：
Adachi M
中科院分区：
文献类型：
--
作者：
Iijima H;Iwano R;Tanaka Y;Muroya K;Fukuda T;Sugie H;Kurosawa K;Adachi M
由GBE 1突变引起的IV型糖原累积病（GSD IV）具有相当广泛的表型变异。虽然经典的肝脏形式和围产期/新生儿神经肌肉形式导致早期死亡，但较轻的表现包括非进行性形式（NP-GSD IV）和成人葡聚糖体病（APBD）。到目前为止，只有一个临床病例的患者与复合杂合突变已报告的NP-GSD IV的分子分析。本研究旨在通过蛋白表达分析阐明NP-GSD IV患者的分子基础，并获得更清晰的GSD IV基因型-表型关系。一名日本男孩在2岁时出现肝脾肿大。发育迟缓、神经症状和心功能不全不明显。在8岁时观察到肝细胞中含有对谷胱甘肽酶耐药的高碘酸-希夫阳性物质，再加上肝脾肿大消退，诊断为NP-GSD IV。红细胞中糖原分支酶活性降低。13岁时，他患上癫痫，通过卡马西平成功控制。在这项研究中，我们确定了复合杂合GBE 1突变（p.Gln46Pro和p.Glu609Lys）。用E.大肠杆菌与淀粉反应。结果表明，两种突变体的活性约为野生型蛋白的50%。这是第二个临床报告的NP-GSD IV患者与明确的分子阐明。基于NP-GSD IV和APBD之间的临床和基因型重叠，我们认为两者处于连续统一体中。
Glycogen storage disease type IV (GSD IV), caused by GBE1 mutations, has a quite wide phenotypic variation. While the classic hepatic form and the perinatal/neonatal neuromuscular forms result in early mortality, milder manifestations include non-progressive form (NP-GSD IV) and adult polyglucosan body disease (APBD). Thus far, only one clinical case of a patient with compound heterozygous mutations has been reported for the molecular analysis of NP-GSD IV. This study aimed to elucidate the molecular basis in a NP-GSD IV patient via protein expression analysis and to obtain a clearer genotype-phenotype relationship in GSD IV. A Japanese boy presented hepatosplenomegaly at 2 years of age. Developmental delay, neurological symptoms, and cardiac dysfunction were not apparent. Observation of hepatocytes with periodic acid-Schiff-positive materials resistant to diastase, coupled with resolution of hepatosplenomegaly at 8 years of age, yielded a diagnosis of NP-GSD IV. Glycogen branching enzyme activity was decreased in erythrocytes. At 13 years of age, he developed epilepsy, which was successfully controlled by carbamazepine. In this study, we identified compound heterozygous GBE1 mutations (p.Gln46Pro and p.Glu609Lys). The branching activities of the mutant proteins expressed using E. coli were examined in a reaction with starch. The result showed that both mutants had approximately 50% activity of the wild type protein. This is the second clinical report of a NP-GSD IV patient with a definite molecular elucidation. Based on the clinical and genotypic overlapping between NP-GSD IV and APBD, we suggest both are in a continuum.
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影响因子：
11.2
作者：
Mochel, Fanny;Schiffmann, Raphael;Steenweg, Marjan E.;Akman, Hasan O.;Wallace, Mary;Sedel, Frederic;Laforet, Pascal;Levy, Richard;Powers, J. Michael;Demeret, Sophie;Maisonobe, Thierry;Froissart, Roseline;Da Nobrega, Bruno Barcelos;Fogel, Brent L.;Natowicz, Marvin R.;Lubetzki, Catherine;Durr, Alexandra;Brice, Alexis;Rosenmann, Hanna;Barash, Varda;Kakhlon, Or;Gomori, J. Moshe;van der Knaap, Marjo S.;Lossos, Alexander
通讯作者：
Lossos, Alexander
影响因子：
3
作者：
Akman, H. Orhan;Karadimas, Charalampos;Petersen, Michael B.
通讯作者：
Petersen, Michael B.
影响因子：
3.4
作者：
Fernandez, Carla;Halbert, Cecile;Pellissier, Jean-Francois
通讯作者：
Pellissier, Jean-Francois
影响因子：
9.9
作者：
Nambu, M;Kawabe, K;Nishino, I
通讯作者：
Nishino, I
影响因子：
9.9
作者：
Bruno, C;van Diggelen, OP;Minetti, C
通讯作者：
Minetti, C