Refinement of the critical region of 1q41q42 microdeletion syndrome identifies FBXO28 as a candidate causative gene for intellectual disability and seizures

Am J Med Genet A. 2014 Feb;164A(2):441-8. doi: 10.1002/ajmg.a.36320. Epub 2013 Dec 19.

Abstract

A clinically recognizable syndrome associated with 1q41q42 microdeletion has recently been described in the literature (OMIM 612530). Patients with microdeletions in this region of chromosome 1 typically have developmental delay, characteristic dysmorphic features, and a predisposition to seizures. Malformations such as congenital diaphragmatic hernia and cleft lip have also been described. There has been considerable interest in mapping the smallest region of overlap for this syndrome in order to identify the critical pathogenic genes. The smallest region of overlap has recently been refined to a region encompassing four genes. Using array comparative genome hybridization (array CGH), we have identified a female with a 590-kB deletion within chromosome1q41q42. This patient's deletion further refines the previously defined region of overlap to a single gene, FBXO28. We propose that FBXO28 is a possible candidate causative gene contributing to the intellectual disability and seizure phenotype observed in 1q41q42 microdeletion syndrome.

Keywords: 1q41q42; Angelman syndrome; Coffin-Siris syndrome; FBXO28; abnormal nails; chromosome deletion; chromosomes; coarse facial features; comparative genomic hybridization; gingival hyperplasia; human; intellectual disability; pair 1; seizure; wide mouth.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 1*
  • Comparative Genomic Hybridization
  • Facies
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • SKP Cullin F-Box Protein Ligases / genetics*
  • Seizures / genetics*
  • Syndrome

Substances

  • FBXO28 protein, human
  • SKP Cullin F-Box Protein Ligases