The first reported patients all had stop mutations in the fifth and last exon of ADNP. Consistent with predicted escape from nonsense mediated decay for mRNA mutations in the last exon, ADNP mRNA levels were not down-regulated in the four available cell lines of patients with stop mutations [Kervestin and Jacobson, 2012; Helsmoortel et al., 2014b]. Unexpectedly, instead of downregulation, overexpression of the ADNP transcripts was observed in these cell lines. Because three of the mutations clustered within basepairs of each other, we were able to discriminate between expression of the mutant and wild type mRNA. Despite the presence of only one copy of the ADNP gene in the genome, this analysis showed unaltered mRNA levels of the wild-type transcript and the excess level of mRNA in these patients corresponds to the amount of mutated mRNA. It would be interesting to see whether the mutated RNA is translated into protein, but Western blots have so far not been reported for these patients. Recently, the expression of the ADNP gene was reported to be auto-regulated by a negative feedback loop mechanism
