Timing in neural maturation: arrest, delay, precociousness, and temporal determination of malformations.

Timing is primordial in initiating and synchronizing each developmental process in tissue morphogenesis. Maturational arrest, delay, and precociousness all are conducive to neurological dysfunction and may determine different malformations depending on when in development the faulty timing occurred, regardless of the identification of a specific genetic mutation or an epigenetic teratogenic event. Delay and arrest are distinguished by whether further progressive development over time can be expected or the condition is static.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus.

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous γH2AX-positive cells in cell lines derived from two affected individuals.