Holoprosencephaly: molecular study of a California population

Am J Med Genet. 2000 Feb 14;90(4):315-9. doi: 10.1002/(sici)1096-8628(20000214)90:4<315::aid-ajmg10>3.0.co;2-y.


Holoprosencephaly (HPE) is a common developmental anomaly of the forebrain and midface in which the cerebral hemispheres fail to separate into distinct left and right halves. HPE is extremely heterogeneous. In addition to teratogenic agents, several genes are implicated in the cause of HPE. Using samples from a population-based birth defects registry in California, we performed a mutational analysis of the known HPE genes Sonic Hedgehog (SHH), ZIC2, and SIX3, in addition to two HPE candidate genes, TG-interacting factor (TGIF), and Patched (PTC), on a group of sporadic HPE patients. This is the first molecular study of HPE in a population-based sample of patients. Among these patients, a deletion in the homeodomain of SIX3 and several polymorphisms in SIX3 and TGIF were identified. No sequence changes were detected in SHH, ZIC2, and PTC. Our results suggest that mutations in the currently recognized HPE genes may explain <5% of all sporadic HPE cases.

Publication types

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

MeSH terms

  • Base Sequence
  • California / epidemiology
  • DNA Primers
  • Exons
  • Eye Proteins
  • Holoprosencephaly / epidemiology
  • Holoprosencephaly / genetics*
  • Homeodomain Proteins / genetics
  • Humans
  • Introns
  • Nerve Tissue Proteins / genetics
  • Polymorphism, Genetic
  • Repressor Proteins*


  • DNA Primers
  • Eye Proteins
  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Repressor Proteins
  • Sine oculis homeobox homolog 3 protein
  • TGIF1 protein, human