A heterozygous microdeletion of 20q13.13 encompassing ADNP gene in a child with Helsmoortel-van der Aa syndrome

Eur J Hum Genet. 2018 Oct;26(10):1497-1501. doi: 10.1038/s41431-018-0165-8. Epub 2018 Jun 13.

Abstract

Helsmoortel-van der Aa (SWI/SNF autism-related or ADNP syndrome) is an autosomal dominant monogenic syndrome caused by de novo variants in the last exon of ADNP gene and no deletions have been documented to date. We report the first case of a 3 years and 10 months old boy exhibiting typical features of ADNP syndrome, including intellectual disability, autistic traits, facial dysmorphism, hyperlaxity, mood disorder, behavioral problems, and severe chronic constipation. 60K Agilent array-comparative genomic hybridization (CGH) identified a heterozygous interstitial microdeletion at 20q13.13 chromosome region, encompassing ADNP and DPM1. Taking into account the clinical phenotype of previously reported cases with ADNP single-point variants, genotype-phenotype correlation in the proband was established and the diagnosis of Helsmoortel-van der Aa syndrome was made. Our report thus confirms that ADNP haploinsufficiency is associated with Helsmoortel-van der Aa syndrome as well as highlights the utility of whole-genome array-CGH for detection of unbalanced submicroscopic chromosomal rearrangements in routine clinical setting in patients with unexplained intellectual disability and/or syndromic autism.

Publication types

  • Case Reports

MeSH terms

  • Autistic Disorder / genetics*
  • Autistic Disorder / physiopathology
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 20 / genetics
  • Comparative Genomic Hybridization
  • Heterozygote
  • Homeodomain Proteins / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Mannosyltransferases / genetics
  • Nerve Tissue Proteins / genetics*
  • Phenotype

Substances

  • ADNP protein, human
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Mannosyltransferases
  • dolichyl-phosphate beta-D-mannosyltransferase