Rare Diseases Symptoms Automatic Extraction

ATRX is required for maintenance of the neuroprogenitor cell pool in the embryonic mouse brain.

[alpha-thalassemia]

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II-IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining the disproportionate layering. Premature differentiation was associated with an increased generation of outer radial glia (oRG) and TBR2-expressing basal progenitors, as well as increased generation of early-born post-mitotic projection neurons. Atrx deletion also reduced the fidelity of mitotic spindle orientation in apical progenitors, where mutant cells were often oriented at non-parallel angles of division relative to the ventricular surface. We conclude that ATRX is required for correct lamination of the mouse neocortex by regulating the timing of neuroprogenitor cell differentiation.

Diseases presenting "developmental delay" symptom

  • 22q11.2 deletion syndrome
  • achondroplasia
  • alexander disease
  • alpha-thalassemia
  • aniridia
  • canavan disease
  • child syndrome
  • classical phenylketonuria
  • coats disease
  • cohen syndrome
  • congenital diaphragmatic hernia
  • congenital toxoplasmosis
  • cowden syndrome
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • hirschsprung disease
  • holt-oram syndrome
  • homocystinuria without methylmalonic aciduria
  • kabuki syndrome
  • kallmann syndrome
  • krabbe disease
  • lamellar ichthyosis
  • monosomy 21
  • neonatal adrenoleukodystrophy
  • phenylketonuria
  • primary hyperoxaluria type 1
  • proteus syndrome
  • pyruvate dehydrogenase deficiency
  • sneddon syndrome
  • triple a syndrome
  • wolf-hirschhorn syndrome
  • zellweger syndrome

This symptom has already been validated