Disruption of the Responsible Gene in a Phosphoglucomutase 1 Deficiency Patient by Homozygous Chromosomal Inversion.
Disruption of the Responsible Gene in a Phosphoglucomutase 1 Deficiency Patient by Homozygous Chromosomal Inversion.
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纯合染色体倒位对磷酸葡萄糖变位酶 1 缺陷患者的负责基因造成破坏。
DOI：
10.1007/8904_2018_108
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kurahashi H.
中科院分区：
文献类型：
--
作者：
Yokoi K;Nakajima Y;Ohye T;Inagaki H;Wada Y;Fukuda T;Sugie H;Yuasa I;Ito T;Kurahashi H.
磷酸葡萄糖变位酶 1 (PGM1) 缺乏症是一种新近定义的疾病，其特征是糖原增多症和由 PGM1 基因隐性突变引起的先天性糖基化障碍。我们报告了一名 12 岁男孩的病例，其父母是表弟，由于肌肉中 PGM1 活性显着降低，他被诊断患有 PGM1 缺乏症。然而，Sanger 测序显示该患者的 PGM1 基因没有致病性突变。由于该病例除了低血糖、转氨酶和肌酸激酶升高外还伴有腭裂，因此进行了核型分析并鉴定出纯合子 inv(1)(p31.1p32.3)。根据PGM1基因在1p31的染色体位置，我们分析了倒位的断点。荧光原位杂交 (FISH) 结合长 PCR 分析显示，倒位破坏了内含子 1 内的 PGM1 基因。由于 PGM1 基因中的起始密码子位于外显子 1 内，我们推测这种倒位使 PGM1 基因失活，从而导致患者的表型。尽管临床和生化诊断呈阳性，但当标准分子检测未能揭示突变时，必须考虑是否存在需要进行核型检查的总体结构变异。
Phosphoglucomutase 1 (PGM1) deficiency is a recently defined disease characterized by glycogenosis and a congenital glycosylation disorder caused by recessive mutations in thePGM1gene. We report a case of a 12-year-old boy with first-cousin parents who was diagnosed with a PGM1 deficiency due to significantly decreased PGM1 activity in his muscle. However, Sanger sequencing revealed no pathogenic mutation in thePGM1gene in this patient. As this case presented with a cleft palate in addition to hypoglycemia and elevated transaminases and creatine kinase, karyotyping was performed and identified homozygous inv(1)(p31.1p32.3). Based on the chromosomal location of thePGM1gene at 1p31, we analyzed the breakpoint of the inversion. Fluorescence in situ hybridization (FISH) combined with long PCR analysis revealed that the inversion disrupts thePGM1gene within intron 1. Since the initiation codon in thePGM1gene is located within exon 1, we speculated that this inversion inactivates thePGM1gene and was therefore responsible for the patient’s phenotype. When standard molecular testing fails to reveal a mutation despite a positive clinical and biochemical diagnosis, the presence of a gross structural variant that requires karyotypic examination must be considered.
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影响因子：
4.2
作者：
Scott, Kyle;Gadomski, Therese;Kozicz, Tamas;Morava, Eva
通讯作者：
Morava, Eva
转铁蛋白和载脂蛋白 C-III 质谱分析用于诊断和筛查先天性糖基化障碍
影响因子：
3
作者：
Y. Wada
通讯作者：
Y. Wada
影响因子：
3.8
作者：
Morava, Eva
通讯作者：
Morava, Eva
通过 1p31 处的新脆弱位点对 1 号染色体上的 PGM1 酶系统和达菲血型进行基因定位
影响因子：
5.3
作者：
J. Herbich;J. Szilvássy;W. Schnedl
通讯作者：
W. Schnedl
影响因子：
3.5
作者：
Timal, Sharita;Hoischen, Alexander;Lefeber, Dirk J.
通讯作者：
Lefeber, Dirk J.