Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment

Hum Genet. 1999 Jan;104(1):108-10. doi: 10.1007/s004390050919.

Abstract

Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large family with recurrence of CS. In addition, the screening of SHH in 7 CS and in 15 sporadic ARM patients with sacral hypodevelopment allowed us to exclude its role in the pathogenesis of these disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anal Canal / abnormalities*
  • Chromosomes, Human, Pair 7 / genetics
  • Digestive System Abnormalities / genetics*
  • Embryonic Induction / genetics
  • Female
  • Hedgehog Proteins
  • Humans
  • Male
  • Pedigree
  • Proteins / genetics*
  • Rectum / abnormalities*
  • Sacrum / abnormalities*
  • Syndrome
  • Trans-Activators*

Substances

  • Hedgehog Proteins
  • Proteins
  • SHH protein, human
  • Trans-Activators