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Epilepsy is one of the most common neurological disorders in humans. Recently, long noncoding RNAs (lncRNAs) have been reported to be important players in neurological diseases. Herein, this study aimed to examine the effect of lncRNA GAS5 on the occurrence of epilepsy in rat and cell models of epileptic seizure. The expression of lncRNA GAS5 was measured in the established rat and cell models. The binding sites between lncRNA GAS5 and miR‐135a‐5p, as well as those between miR‐135a‐5p and 3′ untranslated region of KCNQ3 were predicted by miRDB and Targetscan, separately, followed by verification using dual‐luciferase reporter gene assay. The expression of miR‐135a‐5p was measured in response to the overexpression of lncRNA GAS5. The mRNA and protein levels of KCNQ3 were examined in response to overexpression of miR‐135a‐5p. Next, the latency of epilepsy and frequency of epileptic seizures were assessed in rats injected with Lv‐shGAS5 and Lv‐miR‐135a‐5p in epileptic seizure model. In the rat and cell models, lncRNA GAS5 was highly expressed when epileptic seizure was induced. The expression of miR‐135a‐5p was decreased by overexpression of lncRNA GAS5. Meanwhile, the mRNA and protein levels of KCNQ3 were decreased in response to knockdown of miR‐135a‐5p. After the treatment of Lv‐shGAS5 and Lv‐miR‐135a‐5p, the average latent period of epilepsy was prolonged and the frequency of seizures was decreased. The key findings of the present study provide evidence emphasizing that lncRNA GAS5 functions as a competitive endogenous RNA of miR‐135a‐5p to increase expression of KCNQ3, and lncRNA GAS5 silencing inhibited the occurrence and progression of epilepsy.

Rationale:Subacute combined degeneration (SCD) is a disease caused by decreased vitamin B12 intake or metabolic disorders. It is more common in the elderly and rarely seen in children. Here, we report 2 pediatric cases of SCD in late-onset cobalamin C (CblC) deficiency.Patient concerns:The patients complained of unsteady gait. Their physical examination showed sensory ataxia. Magnetic resonance imaging showed classic manifestations of SCD. The serum vitamin B12 level was normal, but urine methylmalonic acid and serum homocysteine levels were high.Diagnosis:The pathogenic gene was confirmed as MMACHC. The 2 patients each had 2 pathogenic mutations C.482 G>A and C.271dupA and C.365A>T and C.609G>A in this gene. They were diagnosed with combined methylmalonic acidemia and homocysteinemia-CblC subtype.Interventions:The patients were treated with methylcobalamin 500 μg intravenous injection daily after being admitted. After the diagnosis, levocarnitine, betaine, and vitamin B12 were added to the treatment.Outcomes:Twelve days after treatment, the boy could walk normally, and his tendon reflex and sense of position returned to normal. The abnormal gait seemed to have become permanent in the girl and she walked with her legs raised higher than normal.Lessons:To the best of our knowledge, this is the first report of 2 cases of isolated SCD in children with late-onset CblC disorder. Doctors should consider that SCD could be an isolated symptom of CblC disorder. The earlier the treatment, the lower the likelihood of sequelae.

BackgroundAlkuraya–Kučinskas syndrome is an autosomal recessive disorder characterized by brain abnormalities associated with cerebral parenchymal underdevelopment, arthrogryposis, club foot, and global developmental delay. Most reported cases were cases of premature termination of pregnancies or neonatal deaths. To date, limited studies of nine surviving patients with global developmental delay and intellectual disability have been reported. In this study, we report another surviving patient.MethodsWhole-exome sequencing was utilized for the proband, and variants were filtered, annotated, and classified. Candidate variants were validated by Sanger sequencing of the proband and his family. The literature was reviewed; the prognosis among different regions and the variant type was analyzed.ResultsA non-synonymous variant [NM_015312.3: exon29: c.4892C>G (p.Pro1631Arg)] was identified and validated in the patient's father. A frameshift duplication [NM_015312.3: exon62: c.10872dupA (p.Arg3625Lysfs*5)] that caused early translation termination was identified in his mother. The literature was reviewed, variants were classified into three regions of KIAA1109, and their survival status was summarized.ConclusionWe reported another survival proband with Alkuraya–Kučinskas syndrome driven by KIAA1109. Our case expands the genotypic spectrum of Alkuraya–Kučinskas syndrome and explored the relationship between the variant region and survival.

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