This article was prepared by a group consisting of both United State Government employees and non-United States Government employees, and as such is subject to 117 U.S.C. Sec. 105.
Mutational analysis of the Sonic Hedgehog gene in 220 newborns with oral clefts in a South American (ECLAMC) population†
Article first published online: 4 JAN 2002
Published 2002 Wiley-Liss, Inc.
American Journal of Medical Genetics
Volume 108, Issue 1, pages 12–15, 15 February 2002
How to Cite
Orioli, I. M., Vieira, A. R., Castilla, E. E., Ming, J. E. and Muenke, M. (2002), Mutational analysis of the Sonic Hedgehog gene in 220 newborns with oral clefts in a South American (ECLAMC) population. Am. J. Med. Genet., 108: 12–15. doi: 10.1002/ajmg.10204
- Issue published online: 16 JAN 2002
- Article first published online: 4 JAN 2002
- Manuscript Accepted: 24 OCT 2001
- Manuscript Received: 22 DEC 2000
- NIH and the Division of Intramural Research. Grant Numbers: HD01218, HD29862
- CNPq, Brazil. Grant Number: 200728/98-9
- FAPERJ, Brazil. Grant Numbers: E-26/170.688/97, E-26/170.442/99
- FUJB, Brazil. Grant Number: 8222-8
- CAPES, Brazil
- PAPES, Fiocruz, Brazil
- ANPICT, Argentina. Grant Number: PICT 4495
- Sonic Hedgehog;
- cleft lip;
- cleft palate
Oral clefts generally have a multifactorial etiology. A number of genes contribute to the formation of the face and palate. Cleft lip and/or palate can occur in pedigrees with autosomal dominant holoprosencephaly due to mutations in Sonic Hedgehog (SHH). In addition, animal models have shown that SHH is involved in face development. We thus examined the human SHH gene in 220 newborn infants with nonsyndromic oral clefts registered by the Estudio Colaborativo Latinoamericano de Malformaciones Congenitas: ECLAMC (Latin American Collaborative Study of Congenital Malformations). We found 15 variant bands in 13 patients with oral clefts, representing five different base changes, all of which were found by sequencing to represent silent polymorphisms. Four occurred in introns. The alteration occurring in an exon, Ser190Ser, may create a consensus sequence for the 3′splice site 6 bp downstream of the original consensus sequence. Thus, we did not identify any clearly disease-causing mutation in SHH in these patients, and conclude that SHH mutations are not a frequent cause of isolated oral clefts in humans. Published 2002 Wiley-Liss, Inc.