Fig. 1

Identification of a heterozygous de novo mutation in the ADNP gene. (A) Facial photograph of the six-year-old child (https://www.adnpfoundation.org/). (B) Schematic representation of the clinical manifestation of the patient with Helsmoortel–Van der Aa syndrome, including autism, severe ID, and epilepsy. (C) DNA sequencing chromatogram of control and patient alleles, confirming a heterozygous nucleotide duplication (c.1676duplA) in the ADNP gene, (D) replacing the histidine at residue 559 with glutamic acid with a frameshift of two amino acids and introduction of a stop codon (p.His559Glnfs*3). (E) ClustalW alignment across multiple species of ADNP amino acids 520–580. Almost all residues of the ADNP protein are highly conserved amongst vertebrates. The arrow (↓) indicates the species-conserved histidine (H) residue, which is altered in the patient to a glutamic acid (Q) residue. The asterisk (*) indicates positions which have a single, fully conserved residue. A colon (:) indicates conservation between amino acid residues of similar properties