■硫胺素代谢功能障碍综合征(THMD)的发生,一种罕见的常染色体隐性遗传病,可能与TPK1和SLC19A3基因中发现的各种突变有关。这种疾病主要表现为共济失调,肌肉张力减退,突发性或亚急性脑病,在婴儿期的早期阶段实现的发展里程碑下降。我们提供了一项调查的结果,该调查涉及来自伊朗的两个人,两人都经历了癫痫发作以及共济失调和张力减退。通过使用下一代测序(NGS)技术发现了潜在的遗传原因,这有助于检测各种遗传疾病的因果变化。
本研究的病例选择是基于从综合遗传服务中心获得的表型和遗传信息。通过应用全外显子组测序(WES)确定了参与者中观察到的问题的遗传基础。随后,使用sanger测序作为验证任何已鉴定的疑似致病变异的手段.
■首例患者出现TPK1基因纯合突变,NM_022445.4:c.224T>A:p。I75N,导致异亮氨酸在75位取代天冬酰胺(p。I75N)。在我们的调查中,患者2表现出纯合变体,NM_025243.4:c.1385dupA:pY462X,在SLC19A3基因内。
■集体,当患者出现共济失调时,脑病,和基底神经节坏死,鉴于及时干预的潜在优势,必须说明硫胺素缺乏。有时,通过及时给予硫胺素剂量来纠正这种缺陷可能是可行的。因此,根据目前的调查结果,这些变异可能有助于THMD患者的诊断和治疗.
UNASSIGNED: The occurrence of thiamine metabolism dysfunction syndrome (THMD), a rare autosomal recessive condition, may be linked to various mutations found in the TPK1 and
SLC19A3 genes. The disease chiefly manifests through ataxia, muscle hypotonia, abrupt or subacute onset encephalopathy, and a decline in developmental milestones achieved during the early stages of infancy. We present findings from an investigation that involved two individuals from Iran, both of whom experienced seizures along with ataxia and hypotonia. The underlying genetic causes were found with the use of next-generation sequencing (NGS) technology, which has facilitated the detection of causal changes in a variety of genetic disorders.
UNASSIGNED: The selection of cases for this study was based on the phenotypic and genetic information that was obtainable from the Center for Comprehensive Genetic Services. The genetic basis for the problems observed among the participants was determined through the application of whole-exome sequencing (WES). Subsequently, sanger sequencing was employed as a means of validating any identified variations suspected to be causative.
UNASSIGNED: The first patient exhibited a homozygous mutation in the TPK1 gene, NM_022445.4:c.224 T > A:p.I75 N, resulting in the substitution of isoleucine for asparagine at position 75 (p.I75 N). In our investigation, patient 2 exhibited a homozygous variant, NM_025243.4:c.1385dupA:pY462X, within the
SLC19A3 gene.
UNASSIGNED: Collectively, when presented with patients showcasing ataxia, encephalopathy, and basal ganglia necrosis, it is essential to account for thiamine deficiency in light of the potential advantages of prompt intervention. At times, it may be feasible to rectify this deficiency through the timely administration of thiamine dosages. Accordingly, based on the results of the current investigation, these variations may be useful for the diagnosis and management of patients with THMD.