Somatic and germline mosaic mutations in the doublecortin gene are associated with variable phenotypes

Am J Hum Genet. 2000 Sep;67(3):574-81. doi: 10.1086/303043. Epub 2000 Jul 27.

Abstract

Mutations in the X-linked gene doublecortin lead to "double cortex" syndrome (DC) in females and to X-linked lissencephaly (XLIS) in males. Because most patients with DC and XLIS are sporadic, representing de novo doublecortin mutations, we considered that some of these patients could be somatic or germline mosaics. Among a population of 20 patients and their families, we found evidence for mosaic doublecortin mutations in 6 individuals. Germline mosaicism was identified in two unaffected women, each with two affected children. Additionally, one affected male with DC was found to be a somatic mosaic, which presumably spared him from the more severe phenotype of lissencephaly. The high rate of mosaicism indicates that there may be a significant recurrence risk for DC/XLIS in families at risk, even when the mother is unaffected.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Base Sequence
  • Brain / abnormalities*
  • Brain / metabolism
  • Child
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Germ-Line Mutation / genetics*
  • Humans
  • Lymphocytes / metabolism
  • Male
  • Microtubule-Associated Proteins*
  • Mosaicism / genetics*
  • Mutation / genetics*
  • Neuropeptides / genetics*
  • Nuclear Family
  • Pedigree
  • Phenotype
  • Syndrome

Substances

  • Microtubule-Associated Proteins
  • Neuropeptides
  • doublecortin protein