title: No evidence of HAND2 involvement in nonsyndromic cleft lip with or without cleft palate.
abstract: Craniofacial morphogenesis is determined by multistep processes involving signalling molecules and transcription factors, which are organised into highly coordinated pathways. Derailment from this intricate network can lead to congenital malformations. Cells migrate from neural crests to populate different structures, such as branchial arches, involved in embryonal orofacial development. The EDN1 pathway is involved in branchial arch development. Gene knockout and knockdown experiments on EDN1 or its downstream effector dHAND resulted in mice that were characterised by craniofacial defects and cleft palate. Our aim was to evaluate whether the transcription factor HAND2 could be implicated in non-syndromic cleft lip with or without cleft palate (CL/P) aetiology. A sample study composed of 39 multiplex Italian pedigrees was enrolled to test linkage between two microsatellite flanking HAND2 locus and CL/P. No evidence of linkage between HAND2 and CL/P was obtained. Indeed, formal levels of exclusion were obtained with different inheritance models. Investigation results did not support a role of HAND2 in CL/P aetiology. Nevertheless a minor contribute of the gene in clefting could not be ruled out.
authors: Department of Histology, Embryology and Applied Biology, Centre of Molecular Genetics, University of Bologna, Via Belmeloro 8, 40126 Bologna, Italy. marcella.martinelli@unibo.it
authors: Marcella
authors: M
authors: Martinelli
authors: Ambra
authors: A
authors: Girardi
authors: Francesca
authors: F
authors: Farinella
authors: Francesco
authors: F
authors: Carinci
authors: Furio
authors: F
authors: Pezzetti
authors: Elisabetta
authors: E
authors: Caramelli
authors: Luca
authors: L
authors: Scapoli
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D005456:Fluorescent Dyes; D005787:Gene Frequency / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005456:Fluorescent Dyes; C498765:HAND2 protein, human