De novo truncating variants in the AHDC1 gene encoding the AT-hook DNA-binding motif-containing protein 1 are associated with intellectual disability and developmental delay

• DOI: 10.1101/mcs.a000562
• Publication Date: 2015-10-05T18:28:38Z
• Authors: Hui Yang; Ganka Douglas; Kristin G. Monaghan; Kyle Retterer; Megan T. Cho; Luis F. Escobar; Megan E. Tucker; Joan Stoler; Lance H. Rodan; Diane Stein; Warren Marks; Gregory M. Enns; Julia Platt; Rachel Cox; Patricia G. Wheeler; Carrie Crain; Amy Calhoun; Rebecca Tryon; Gabriele Richard; Patrik Vitazka; Wendy K. Chung
• Keywords: Sanger sequencing; Speech delay

Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies genetic etiology up to 30% of cases intellectual disability (ID). Using WES, we identified seven unrelated patients with similar phenotype severe or neurodevelopmental delay who were all heterozygous for de novo truncating variants the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The minimally verbal nonverbal had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, self-injurious behaviors. Additional common features include dysmorphic facial feeding difficulties associated failure thrive short stature. AHDC1 gene has only one coding exon, contains conserved regions motifs PDZ binding domain. We postulate that detected these result truncated missing critical functional domains, disrupting interactions other proteins important brain development. Our study demonstrates are ID primarily phenotype.