Çakar Nafiye Emel, Gezdirici Alper, Topuz Hanım Şeyma, Önal Hasan
Division of Pediatric Metabolism, Okmeydanı Training and Research Hospital, University of Health Sciences, İstanbul, Turkey.
Division of Medical Genetics, Kanuni Sultan Süleyman Training and Research Hospital, University of Health Sciences, İstanbul, Turkey.
Pediatr Int. 2020 Oct;62(10):1145-1150. doi: 10.1111/ped.14286. Epub 2020 Sep 28.
Glycogen storage diseases (GSD) are disorders of autosomal recessive carbohydrate metabolism, characterized by glycogen accumulation. The liver and muscle tissue are commonly affected but patients may present with different clinical manifestations. The presence of glycogen can be demonstrated in biopsies and definitive diagnosis can be made by enzymatic or molecular analysis. The aim of this study was to determine specific gene mutations in our cases with GSD.
Thirty-eight patients with clinical and laboratory diagnoses of GSD were studied. Thirty-two patients had undergone genetic analysis. In our study, a next-generation sequencing panel was used.
Five novel variants of uncertain significance (VUS), which were likely to be pathogenic, were detected in seven patients. Two new pathogenic variations of c.927delT (p.Phe309LeufsTer4) homozygous and c.44C>G (p.Ser15Ter) homozygous in the G6PC gene were detected in two GSD type Ia patients. In our two non-sibling GSD type III patients, c.1439T>G (p.Leu480Arg) homozygous novel-VUS was detected in the AGL gene. In our GSD type IV patient, c.1054G>C (p.Asp352His) homozygous novel-VUS was detected in the GBE1 gene. In GSD type VI, two sibling patients had a c.1454A>G (p.Asn485Ser) homozygous novel-VUS change in the PYGL gene.
We determined the gene mutations specific to cohorts in our cases with GSD. The novel pathogenic, likely pathogenic, and VUS changes identified will contribute to the relationship between the patients' clinical and laboratory findings.
糖原贮积病（GSD）是常染色体隐性碳水化合物代谢紊乱疾病，其特征为糖原蓄积。肝脏和肌肉组织常受影响，但患者可能表现出不同的临床表现。活检中可证实糖原的存在，通过酶学或分子分析可做出明确诊断。本研究的目的是确定我们的糖原贮积病病例中的特定基因突变。
对38例临床和实验室诊断为糖原贮积病的患者进行了研究。32例患者接受了基因分析。在我们的研究中，使用了下一代测序面板。
在7例患者中检测到5个意义未明的新变异（VUS），这些变异可能具有致病性。在2例Ia型糖原贮积病患者中检测到G6PC基因的两个新的致病性变异，即纯合的c.927delT（p.Phe309LeufsTer4）和纯合的c.44C>G（p.Ser15Ter）。在我们的2例非亲缘关系的III型糖原贮积病患者中，在AGL基因中检测到纯合的新VUS c.1439T>G（p.Leu480Arg）。在我们的IV型糖原贮积病患者中，在GBE1基因中检测到纯合的新VUS c.1054G>C（p.Asp352His）。在VI型糖原贮积病中，2例同胞患者在PYGL基因中有纯合的新VUS变化c.1454A>G（p.Asn485Ser）。
我们确定了我们的糖原贮积病病例队列特有的基因突变。所鉴定的新的致病性、可能致病性和意义未明的变异将有助于阐明患者临床和实验室检查结果之间的关系。
