Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes

Am J Hum Genet. 1999 Jan;64(1):118-25. doi: 10.1086/302214.

Abstract

In Williams syndrome (WS), a deletion of approximately 1.5 Mb on one copy of chromosome 7 causes specific physical, cognitive, and behavioral abnormalities. Molecular dissection of the phenotype may be a route to identification of genes important in human cognition and behavior. Among the genes known to be deleted in WS are ELN (which encodes elastin), LIMK1 (which encodes a protein tyrosine kinase expressed in the developing brain), STX1A (which encodes a component of the synaptic apparatus), and FZD3. Study of patients with deletions or mutations confined to ELN showed that hemizygosity for elastin is responsible for the cardiological features of WS. LIMK1 and STX1A are good candidates for cognitive or behavioral aspects of WS. Here we describe genetic and psychometric testing of patients who have small deletions within the WS critical region. Our results suggest that neither LIMK1 hemizygosity (contrary to a previous report) nor STX1A hemizygosity is likely to contribute to any part of the WS phenotype, and they emphasize the importance of such patients for dissecting subtle but highly penetrant phenotypes.

Publication types

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

MeSH terms

  • Adult
  • Antigens, Surface / genetics
  • Child
  • Chromosome Mapping
  • Chromosomes, Human, Pair 7*
  • DNA-Binding Proteins / genetics
  • Elastin / genetics
  • Female
  • Frizzled Receptors
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intelligence / genetics*
  • Lim Kinases
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Phenotype
  • Polymerase Chain Reaction
  • Protein Kinases
  • Protein Serine-Threonine Kinases / genetics
  • Receptors, Cell Surface / genetics
  • Receptors, G-Protein-Coupled*
  • Sequence Deletion
  • Spatial Behavior
  • Syntaxin 1
  • Visual Perception
  • Williams Syndrome / genetics*
  • Williams Syndrome / physiopathology
  • Zinc Fingers / genetics

Substances

  • Antigens, Surface
  • DNA-Binding Proteins
  • FZD3 protein, human
  • Frizzled Receptors
  • Nerve Tissue Proteins
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • STX1A protein, human
  • Syntaxin 1
  • Elastin
  • Protein Kinases
  • LIMK1 protein, human
  • Lim Kinases
  • Protein Serine-Threonine Kinases