PDF(Pubmed)
Abstract：
UNASSIGNED: SLC13A5 (solute carrier family 13, member 5) encodes sodium/citrate cotransporter, which mainly localizes in cellular plasma membranes in the frontal cortex, retina, and liver. Pathogenic variants of the gene cause an autosomal recessive syndrome known as \"developmental and epileptic encephalopathy 25 with amelogenesis imperfecta.\"
UNASSIGNED: Here, we have investigated six patients from three different consanguineous Saudi families. The affected individuals presented with neonatal seizures, developmental delay, and significant defects in tooth development. Some patients showed other clinical features such as muscle weakness, motor difficulties, intellectual disability, microcephaly, and speech problems in addition to additional abnormalities revealed by electroencephalography (EEGs) and magnetic resonance imaging (MRI). One of the MRI findings was related to cortical thickening in the frontal lobe. To diagnose and study the genetic defects of the patients, whole exome sequencing (WES) coupled with confirmatory Sanger sequencing was utilized. Iterative filtering identified two variants of SLC13A5, one of which is novel, in the families. Families 1 and 2 had the same insertion (a previously reported mutation), leading to a frameshift and premature stop codon. The third family had a novel splice site variant. Confirmatory Sanger sequencing corroborated WES results and indicated full segregation of the variants in the corresponding families. The patients\' conditions were poorly controlled by multiple antiepileptics as they needed constant care.
UNASSIGNED: Considering that recessive mutations are common in the Arab population, SLC13A5 screening should be prioritized in future patients harboring similar symptoms including defects in molar development.
UNASSIGNED: Here, we have investigated six patients from three different consanguineous Saudi families. The affected individuals presented with neonatal seizures, developmental delay, and significant defects in tooth development. Some patients showed other clinical features such as muscle weakness, motor difficulties, intellectual disability, microcephaly, and speech problems in addition to additional abnormalities revealed by electroencephalography (EEGs) and magnetic resonance imaging (MRI). One of the MRI findings was related to cortical thickening in the frontal lobe. To diagnose and study the genetic defects of the patients, whole exome sequencing (WES) coupled with confirmatory Sanger sequencing was utilized. Iterative filtering identified two variants of SLC13A5, one of which is novel, in the families. Families 1 and 2 had the same insertion (a previously reported mutation), leading to a frameshift and premature stop codon. The third family had a novel splice site variant. Confirmatory Sanger sequencing corroborated WES results and indicated full segregation of the variants in the corresponding families. The patients\' conditions were poorly controlled by multiple antiepileptics as they needed constant care.
UNASSIGNED: Considering that recessive mutations are common in the Arab population, SLC13A5 screening should be prioritized in future patients harboring similar symptoms including defects in molar development.
摘要：
未经授权：SLC13A5（溶质载体家族13，成员5）编码钠/柠檬酸共转运蛋白，主要位于额叶皮质的细胞质膜中，视网膜,还有肝脏.该基因的致病变异导致常染色体隐性综合征，称为发育性和癫痫性脑病25，伴有牙釉质发育不全症。\"
未经批准：这里，我们调查了来自三个不同血缘关系的沙特家庭的6名患者.受影响的个体出现新生儿癫痫发作，发育迟缓,和牙齿发育的显著缺陷。一些患者表现出其他临床特征，如肌肉无力，电机困难，智力残疾,小头畸形,和言语问题，以及脑电图（EEG）和磁共振成像（MRI）显示的其他异常。MRI发现之一与额叶皮质增厚有关。诊断和研究患者的遗传缺陷，采用全外显子组测序(WES)结合验证性Sanger测序.迭代滤波确定了SLC13A5的两个变体，其中一个是新颖的，在家庭中。家族1和2具有相同的插入（先前报道的突变），导致移码和过早的终止密码子。第三个家族有一个新的剪接位点变异体。验证性Sanger测序证实了WES结果并表明相应家族中变体的完全分离。由于需要持续护理，多种抗癫痫药对患者的病情控制不佳。
UNASSIGNED：考虑到隐性突变在阿拉伯人口中很常见，SLC13A5筛查应优先考虑未来有类似症状的患者，包括磨牙发育缺陷。
未经批准：这里，我们调查了来自三个不同血缘关系的沙特家庭的6名患者.受影响的个体出现新生儿癫痫发作，发育迟缓,和牙齿发育的显著缺陷。一些患者表现出其他临床特征，如肌肉无力，电机困难，智力残疾,小头畸形,和言语问题，以及脑电图（EEG）和磁共振成像（MRI）显示的其他异常。MRI发现之一与额叶皮质增厚有关。诊断和研究患者的遗传缺陷，采用全外显子组测序(WES)结合验证性Sanger测序.迭代滤波确定了SLC13A5的两个变体，其中一个是新颖的，在家庭中。家族1和2具有相同的插入（先前报道的突变），导致移码和过早的终止密码子。第三个家族有一个新的剪接位点变异体。验证性Sanger测序证实了WES结果并表明相应家族中变体的完全分离。由于需要持续护理，多种抗癫痫药对患者的病情控制不佳。
UNASSIGNED：考虑到隐性突变在阿拉伯人口中很常见，SLC13A5筛查应优先考虑未来有类似症状的患者，包括磨牙发育缺陷。
