title: Mutational analysis of the Sonic Hedgehog gene in 220 newborns with oral clefts in a South American (ECLAMC) population.
abstract: 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.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors.forename: Iêda M
authors.initials: IM
authors.lastname: Orioli
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Vieira
authors.forename: Eduardo E
authors.initials: EE
authors.lastname: Castilla
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Ming
authors.forename: Maximilian
authors.initials: M
authors.lastname: Muenke
mesh_terms: D000818:Animals; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D053823:Hedgehog Proteins; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D011110:Polymorphism, Genetic; D013020:South America; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins; C509239:SHH protein, human; D015534:Trans-Activators