RESUMEN
Subcortical band heterotopia (SHB) is a rare severe brain developmental malformation caused by deficient neuronal migration during the development of cerebral cortex. Here, a human induced pluripotent stem cell (iPSCs) line was established from a 4-year-1-month-old girl with SHB carrying a heterozygous mutation (c.568A > G, p.K190E) in DCX. The generated iPSC line showed the ability to differentiate into three lineages in vitro and was confirmed by pluripotency markers and the original gene mutation.
Asunto(s)
Lisencefalias Clásicas y Heterotopias Subcorticales en Banda , Células Madre Pluripotentes Inducidas , Femenino , Humanos , Lactante , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/genética , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Mutación/genética , Heterocigoto , Corteza CerebralRESUMEN
Introduction: Subcortical band heterotopia (SBH) is a rare brain developmental malformation caused by deficient neuronal migration during embryogenesis. Published literature on pediatric SBH cases caused by DCX mutations is limited. Methods: The detailed clinical and genetic features of two pediatric SBH with DCX mutations were analyzed. The available literature on DCX mutations was reviewed. Results: Both patients were girls with varying degrees of developmental delay. Patient 1 was short in stature with peculiar facial features. Patient 2 had an early seizure onset and developed drug-resistant epilepsy. Whole-exome sequencing (WES) revealed two de novo heterozygous variants of DCX (NM_178153.3), including a novel missense variant of c.568A > G (p.K190E) in P1 and a reported nonsense variant of c.814C > T (p.R272*) in P2. We reviewed all the available literature regarding DCX mutations. A total of 153 different mutations have been reported, with the majority of 99 (64.7 %) being missense mutations. Conclusion: Our study expanded the mutational spectrum of DCX, which has important implications for the study of genotype-phenotype correlations. Furthermore, it provided insights to better understand SBH and genetic counseling.
RESUMEN
AUTS2 syndrome is a neurodevelopmental disorder caused by pathogenic variants and deletions of the AUTS2 gene, resulting in intellectual disability, microcephaly, and other phenotypes. Here, we generated a human induced pluripotent stem cell (iPSC) line from a 21-month-old boy with AUTS2 syndrome caused by a heterozygous mutation (c.1486C > T, p.Q496X) in the AUTS2 gene. The iPSCs had normal morphology and karyotype, expressed pluripotency markers, showed differentiation potential in vitro, and carried the AUTS2 gene mutation.
Asunto(s)
Células Madre Pluripotentes Inducidas , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Masculino , Humanos , Lactante , Células Madre Pluripotentes Inducidas/metabolismo , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Mutación/genética , Diferenciación Celular , Proteínas del Citoesqueleto/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
In this study, peripheral blood mononuclear cells were isolated from a young male patient bearing a histone deacetyl-lase 8 (HDAC8) mutation and suffering from Cornelia de Lange Syndrome verified by clinical and genetic diagnosis. Induced pluripotent stem cells (iPSCs) were established by a non-integrative method, using plasmids carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSCs presented typical pluripotent cells morphology, and expressed pluripotent stem cell markers at the mRNA and protein level. The iPSCs also showed differentiative capacity in vitro, and a normal karyotype. In addition, the established iPSCs still carried the HDAC8 mutation observed in the donor tissue.