Interstitial deletion 5q14.3q21.3 with MEF2C haploinsufficiency and mild phenotype: when more is less

Am J Med Genet A. 2011 Jun;155A(6):1437-41. doi: 10.1002/ajmg.a.34012. Epub 2011 May 12.

Abstract

An 18-year-old female with mild mental disability (global IQ 69), febrile seizures with subsequent myoclonic/grand mal epilepsy, and subtle morphologic changes is described with del 5(q14.3q21.3) by karyotype and minimal DNA deletion of 21.08 Mb by array comparative genomic hybridization microarray analysis (arr chr5:83,592,798-104,671,993 X1) that encompasses at least 50 genes. Included in the deletion interval is the MEF2C gene that usually causes severe mental disability when haploinsufficient, illustrating the complexity of clinic-cytogenetic correlation even with defined segmental aneuploidy. Interaction of MEF2C with the deleted febrile seizure (FEB4) and juveline myoclonic epilepsy (EJM4) loci plus the G-protein receptor (GPR98/MASS1/Usher syndrome) gene may moderate the phenotype, perhaps through common regulation by calcium.

MeSH terms

  • Adolescent
  • Chromosome Deletion*
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / pathology*
  • Chromosomes, Human, Pair 5 / genetics*
  • Comparative Genomic Hybridization
  • Epilepsy / pathology
  • Female
  • Haploinsufficiency / genetics*
  • Humans
  • Karyotyping
  • MADS Domain Proteins / genetics*
  • MADS Domain Proteins / metabolism
  • MEF2 Transcription Factors
  • Myogenic Regulatory Factors / genetics*
  • Myogenic Regulatory Factors / metabolism
  • Phenotype*
  • Receptors, G-Protein-Coupled / metabolism
  • Seizures, Febrile / pathology

Substances

  • ADGRV1 protein, human
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • MEF2C protein, human
  • Myogenic Regulatory Factors
  • Receptors, G-Protein-Coupled