RESUMEN

Background: Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia (NEDSCAC), induced by MED27 gene, is an autosomal recessive rare disorder characterized by widespread developmental delay with varying degrees of intellectual impairment. Other symptoms include limb spasticity, cataracts, and cerebellar hypoplasia. So far there have been limited reports on NEDSCAC. Methods: In this study, we conducted genetic testing on a child presenting with developmental delay as the primary clinical feature. The genetic test results indicated the presence of novel homozygous missense variants c.74G > A, p.(Arg25His) in the MED27 gene. In vitro functional validation experiments, including plasmid construction and cell transfection, Western blotting, and molecular dynamics structural modeling, were performed on the MED27 Arg25His variant. Results: The results demonstrated a significant reduction in protein expression of MED27 Arg25His and indicated may weaken the interaction force between the MED27 subunit and MED14 subunit. Conclusions: This study expands our understanding of MED27 gene variants and their associated clinical phenotypes. Additionally, it contributes to the investigation of the potential pathogenesis of NEDSCAC caused by MED27 gene variants.

RESUMEN

BACKGROUND: Lamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF. METHODS: This study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF. RESULTS: Three of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein. CONCLUSIONS: Through a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

Asunto(s)

Factores de Transcripción SOXD , Humanos , Masculino , Femenino , China , Factores de Transcripción SOXD/genética , Preescolar , Niño , Estudios Retrospectivos , Secuenciación del Exoma , Mutación/genética , Lactante , Discapacidad Intelectual/genética , Discapacidades del Desarrollo/genética

RESUMEN

Objective: This study aims to describe the characteristics of the brain network attributes in children diagnosed with Infantile Epileptic Spasms Syndrome (IESS) and to determine the influence exerted by adrenocorticotrophic hormone (ACTH) or methylprednisolone (MP) on network attributes. Methods: In this retrospective cohort study, we recruited 19 infants diagnosed with IESS and 10 healthy subjects as the control from the Pediatric Neurology Department at the Third Affiliated Hospital of Zhengzhou University between October 2019 and December 2020. The first thirty-minute processed electroencephalograms (EEGs) were clipped and filtered into EEG frequency bands (2 s each). A comparative assessment was conducted between the IESS group and the controls as well as the pre- and post-treatment in the IESS group. Mutual information values for each EEG channel were collected and compared including characteristic path length (CPL), node degree (ND), clustering coefficient (CC), and betweenness centrality (BC), based on graph theory. Results: Comparing the control group, in the IESS group, there was an increase in CPL of the Delta band, and a decrease in ND and CC of the Delta band during the waking period, contrary to those during the sleeping period (P < 0.05), a decreased in CPL of the fast waves and an increase in ND and CC (P < 0.05) in the sleep-wake cycle, and a decrease in ND and CC of the Theta band in the waking phase. Post-treatment compared with the pre-treatment, during the waking ictal phase, there was a noted decrease in CPL in the Delta band and fast waves, while an increase was observed in ND and CC (P < 0.05). Conclusions: The Delta band and fast waves are crucial components of the network attributes in IESS. Significance: This investigation provides a precise characterization of the brain network in children afflicted with IESS, and lays the groundwork for predicting the prognosis using graph theory.