A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia
A common mutation in the COG7 gene with a consistent phenotype including microcephaly, adducted thumbs, growth retardation, VSD and episodes of hyperthermia
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DOI：
10.1038/sj.ejhg.5201813
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发表时间：
2007-06-01
影响因子：
5.2
通讯作者：
Wevers, Ron A.
中科院分区：
文献类型：
--
作者：
Morava, Eva;Zeevaert, Renate;Wevers, Ron A.
我们描述了来自两个不同家系的三名患者的临床和生化特征，诊断为先天性IIe型糖基化障碍，原因是保守的寡聚体高尔基复合体(COG)7缺陷，COG是COG的八个亚基之一。近亲父母的兄弟姐妹和1名独生子女表现为生长迟缓、进行性小头畸形、严重小头畸形、低眼压、拇指内收、胃肠道假性梗阻、进食困难、发育不良、心脏异常、皮肤皱纹和极端高温发作。在N-和O-连接的糖基化和低催化的生物合成中检测到一种组合的紊乱。Western印迹分析显示COG5和COG7亚基严重减少。在所有患者中都发现了COG7基因的纯合子内含子剪接点突变(C.169+4A>；C)。除了我们的患者没有骨骼异常和只有轻微的肝脏受累外，表型与之前描述的两名具有相同突变的北非裔患者相似。我们建议对进行性小头畸形、生长迟缓、低眼压、拇指内收和心脏缺陷的患者，特别是与皮肤异常或高热相关的患者，进行COG不同亚基的蛋白质糖基化研究和蛋白质印迹。这种特征表型的存在可能需要直接的DNA分析。
We describe the clinical and biochemical characteristics in three patients from two different families diagnosed with Congenital Disorder of Glycosylation type IIe owing to a defect in Conserved Oligomeric Golgi complex ( COG) 7; one of the eight subunits of the COG. The siblings and an unrelated single child of consanguineous parents presented with growth retardation, progressive, severe microcephaly, hypotonia, adducted thumbs, feeding problems by gastrointestinal pseudo-obstruction, failure to thrive, cardiac anomalies, wrinkled skin and episodes of extreme hyperthermia. A combined disorder in the biosynthesis of N- and O-linked glycosylation with hyposialylation was detected. Western blot analysis showed a severe reduction in the COG5 and 7 subunits of the COG. A homozygous, intronic splice site mutation (c.169 + 4A > C) of the COG7 gene was identified in all patients. The phenotype is similar to that previously described in two patients of North African ethnicity with the same mutation, except for the lack of skeletal anomalies and only a mild liver involvement in our patients. We suggest performing protein glycosylation studies and Western blot for the different COG subunits in patients with progressive microcephaly, growth retardation, hypotonia, adducted thumbs and cardiac defects, especially in association with skin anomalies or episodes of hyperthermia. The presence of the characteristic phenotype might warrant direct DNA analysis.