Jezela-Stanek Aleksandra, Blaz Witold, Gora Artur, Bochenska Malgorzata, Kusmierska Katarzyna, Sykut-Cegielska Jolanta
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland.
Clinical Department of Neonatology and NICU, Saint Jadwiga the Queen Clinical Provincial Hospital No2, 35-301 Rzeszow, Poland.
Diagnostics (Basel). 2020 Oct 14;10(10):821. doi: 10.3390/diagnostics10100821.
(1) Background: Molybdenum cofactor deficiency type B (MOCODB, #252160) is a rare autosomal recessive metabolic disorder characterized by intractable seizures of neonatal-onset, muscular spasticity, accompanying with hypouricemia, elevated urinary sulfite levels and craniofacial dysmorphism. Thirty-five patients were reported to date. (2) Methods: Our paper aimed to delineate the disease genotype by presenting another patient, in whom a novel, in-frame variant within the gene was identified. (3) Results: Exome sequencing led to the identification of a novel variant in the gene-c.472_477del of unknown significance (VUS). (4) Conclusions: To prove the clinical significance of the mentioned variant, analysis of the possible mutation consequences on molecular level with the use of the available crystal structure of the human molybdopterin synthase complex was of great importance. Moreover, a potential pathomechanism resulting from a molecular defect was presented, giving original insight into the current knowledge on this rare disease, including treatment options.
(1) 背景：B型钼辅因子缺乏症（MOCODB，#252160）是一种罕见的常染色体隐性代谢紊乱疾病，其特征为新生儿期起病的顽固性癫痫、肌肉痉挛，伴有低尿酸血症、尿亚硫酸盐水平升高和颅面畸形。迄今为止，已报道35例患者。(2) 方法：我们的论文旨在通过介绍另一例患者来描绘该疾病的基因型，在该患者中鉴定出了该基因内一个新的框内变异。(3) 结果：外显子组测序导致在该基因中鉴定出一个新的变异——c.472_477del，其意义不明（VUS）。(4) 结论：为证明上述变异的临床意义，利用人钼蝶呤合酶复合物的现有晶体结构在分子水平分析可能的突变后果非常重要。此外，还提出了由分子缺陷导致的潜在发病机制，为目前关于这种罕见疾病的知识（包括治疗选择）提供了独到见解。
