Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome, characterized by nevus sebaceous,central nervous system (CNS), ocular and skeletal abnormalities. The present study describes KRAS somatic mosaic mutation in a case of LNSS with lymphatic malformations (LMs). A 4-month-old female with a clinical diagnosis of LNSS presented with infantile spasms, mental retardation, skull dysplasia, ocular abnormalities, congenital atrial septal defect, and LMs. Cervical ultrasonography revealed a 4.6 × 4.6 × 2.2cm no echo packet with clear boundary in the subcutaneous tissues of the right neck. The neck MRI indicated a cyst in the subcutaneous tissues of the right neck. Whole-exome sequencing revealed a low-level heterozygous mutation of the KRAS gene (c.35C > T; p.G12D, 19%) in the skin lesion sample. This mutation was not present in the blood samples of the patient and her parents. The patient received sclerotherapy with paicibanil (OK-432) injection for the cyst. Following 1 year of treatment, the patient exhibited fewer seizures. The mental and motor development was significantly improved. The patient can currently walk with assistance and speak simple words. LNSS is a rare, congenital neurocutaneous syndrome consisting of a spectrum of abnormalities involving the skin, central nervous system, eyes, LMs and other systems. LNSS can be caused by postzygotic somatic mutation in the RAS family of genes. Multidisciplinary evaluation and treatment is needed.

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders. Genetically based subtype identification may prove more beneficial not only in illuminating the course and prognosis, but also for individualized treatment targets of an ASD sub-group. Increasing evidence has shown that de novo loss-of-function mutations in the chromodomain helicase DNA-binding protein 8 (CHD8) gene are associated with an ASD sub-group. Here we describe two ASD cases in children with mild intellectual disability, early motor deficits, and speech delay, without distinct structural or EEG brain anomalies. Exome sequencing revealed a novel heterozygous nonsense/missense mutations(c.2647C > A/p.E883X and c.1677C > A/p.M559I respectively) in CHD8 gene. There were few cases in the literature reporting de novo mutation of CHD8 in ASD. As demonstrated in our patients, along with other previously reported studies support that disruption of the CHD8 gene represents a specific genetic sub-type of ASD.

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation.Methods: We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein–protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior.Results: We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring.Conclusions: Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.