CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter)
CDG-Id caused by homozygosity for an ALG3 mutation due to segmental maternal isodisomy UPD3(q21.3-qter)
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DOI：
10.1016/j.ejmg.2005.01.002
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发表时间：
2005-04-01
影响因子：
1.9
通讯作者：
Matthijs, G
中科院分区：
文献类型：
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作者：
Schollen, E;Grünewald, S;Matthijs, G
我们报告一个病人的先天性糖基化型Id（CDG-Id）的ALG 3基因，这是从一个从头突变与一个节段性母亲单亲异二体性（UPD）相结合的结果纯合突变引起的。患者表现为严重的精神发育迟滞、原发性小头畸形和视神经萎缩，与严重形式的CDG相一致。转铁蛋白的等电聚焦显示I型模式，并且脂质连接寡糖分析显示dol-PP-GlcNAC（2）Man（5）在患者的成纤维细胞中积累，表明ALG 3基因中存在缺陷。鉴定了纯合ALG 3错义突变p.R266C（c.796C > T）。进一步的评估显示，母亲和父亲都不是p.R266C突变的携带者。标记物分析显示染色体3q21.3-3qter区域的节段性母系同二体性。该区域的UPD以前没有描述过。更重要的是，UPD与新生突变的结合是一种特殊的巧合和非凡的观察。(c)2005年，Elsevier SAS。All rights reserved.
We report on a patient with a congenital disorder of glycosylation type Id (CDG-Id) caused by a homozygous mutation in the ALG3 gene, which results from a de novo mutation in combination with a segmental maternal uniparental isodisomy (UPD). The patient presented with severe psychomotor delay, primary microcephaly, and opticus atrophy, compatible with a severe form of CDG. Isoelectric focusing of transferrin showed a type I pattern and lipid-linked oligosaccharide analysis showed an accumulation of dol-PP-GlcNAC(2)Man(5), in patient's fibroblasts suggesting a defect in the ALG3 gene. A homozygous ALG3 missense mutation p.R266C (c.796C > T) was identified. Further evaluation revealed that neither the mother nor the father were carrier of the p.R266C mutation. Marker analysis revealed a segmental maternal isodisomy for the chromosomal region 3q21.3-3qter. UPD for this region has not been described before. More important, the combination of UPD with a de novo mutation is an exceptional coincidence and an extraordinary observation. (c) 2005 Elsevier SAS. All rights reserved.