Cleft lip with or without cleft palate: implication of the heavy chain of non-muscle myosin IIA

Marcella Martinelli ¹, Mariateresa Di Stazio ², Luca Scapoli ¹, Jlenia Marchesini ³, Filomena Di Bari ⁴, Furio Pezzetti ¹, Francesco Carinci ^5*, Annalisa Palmieri ¹, Paolo Carinci ¹ and Anna Savoia ²

¹ Department of Histology, Embryology and Applied Biology, University of Bologna, Italy
² Medical Genetics, Department of Reproductive and Developmental Sciences, IRCCS, Italy
³ Department of Morphology and Embryology, Section of Histology and Embryology, University of Ferrara, Italy
⁴ Telethon Institute of Genetics and Medicine, Italy
⁵ Chair of Maxillo-Facial Surgery, University of Ferrara, Italy

^* To whom correspondence should be addressed. E-mail: crc{at}unife.it.

Accepted 14 February 2007

Abstract

Non-syndromic cleft lip with or without palate (CL/P) is one of the most common malformations among live births but most of the genetic components and environmental factors involved remain to be identified. Among the different causes, we considered MYH9, the gene encoding for the heavy chain of non-muscle myosin IIA, as a potential candidate because we found it abundantly and specifically expressed in epithelial cells of palatal shelves before fusion. After fusion we showed that, its expression level decreases and becomes limited to epithelial triangles before disappearing as fusion is completed. In order to understand whether MYH9 plays a role in CL/P etiology, a family-based association analysis was performed in 218 case/parent triads using SNP markers. Pairwise and multi-locus haplotype analyses identified linkage disequilibrium between polymorphism alleles at the MYH9 locus and the disease. The strongest deviation from a null hypothesis of random sharing was obtained with two adjacent SNPs, rs3752462 and rs2009930, (global P value = .00001), indicating that MYH9 might be a predisposing factor for CL/P, though its pathogenetic role needs to be more accurately investigated.

Keywords: Cleft lip, gene expression, linkage disequilibrium, nonmuscle myosin IIA, single nucleotide polymorphism

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