Transcriptome analysis of MBD5-associated neurodevelopmental disorder (MAND) neural progenitor cells reveals dysregulation of autism-associated genes

Sci Rep. 2021 May 28;11(1):11295. doi: 10.1038/s41598-021-90798-z.


MBD5-associated neurodevelopmental disorder (MAND) is an autism spectrum disorder (ASD) characterized by intellectual disability, motor delay, speech impairment and behavioral problems; however, the biological role of methyl-CpG-binding domain 5, MBD5, in neurodevelopment and ASD remains largely undefined. Hence, we created neural progenitor cells (NPC) derived from individuals with chromosome 2q23.1 deletion and conducted RNA-seq to identify differentially expressed genes (DEGs) and the biological processes and pathways altered in MAND. Primary skin fibroblasts from three unrelated individuals with MAND and four unrelated controls were converted into induced pluripotent stem cell (iPSC) lines, followed by directed differentiation of iPSC to NPC. Transcriptome analysis of MAND NPC revealed 468 DEGs (q < 0.05), including 20 ASD-associated genes. Comparison of DEGs in MAND with SFARI syndromic autism genes revealed a striking significant overlap in biological processes commonly altered in neurodevelopmental phenotypes, with TGFβ, Hippo signaling, DNA replication, and cell cycle among the top enriched pathways. Overall, these transcriptome deviations provide potential connections to the overlapping neurocognitive and neuropsychiatric phenotypes associated with key high-risk ASD genes, including chromatin modifiers and epigenetic modulators, that play significant roles in these disease states.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / metabolism
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / metabolism
  • Autistic Disorder / genetics
  • Cell Differentiation / genetics
  • Chromosome Deletion
  • Chromosomes, Human, Pair 2 / genetics
  • Chromosomes, Human, Pair 2 / metabolism
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression / genetics
  • Gene Expression Profiling / methods
  • Humans
  • Induced Pluripotent Stem Cells / metabolism
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism
  • Neural Stem Cells / metabolism
  • Neurodevelopmental Disorders / genetics*
  • Neurodevelopmental Disorders / metabolism
  • Phenotype
  • Primary Cell Culture
  • RNA-Seq
  • Signal Transduction / genetics
  • Transcriptome / genetics


  • DNA-Binding Proteins
  • MBD5 protein, human

Supplementary concepts

  • Chromosome 2q31.2 Deletion Syndrome