Mutation Distribution and Type Suggests Genetic Differences between the Etiology of Orofacial Clefting and Gastric Cancer.

Pathogenic variants in , encoding epithelial cadherin (E-cadherin), have been implicated in hereditary diffuse gastric cancer (HDGC), lobular breast cancer, and both syndromic and non-syndromic cleft lip/palate (CL/P). Despite the large number of mutations described, the nature of the phenotypic consequence of such mutations is currently not able to be predicted, creating significant challenges for genetic counselling. This study collates the phenotype and molecular data for available variants that have been classified, using the American College of Medical Genetics and Genomics criteria, as at least 'likely pathogenic', and correlates their molecular and structural characteristics to phenotype.

Potential Risk for Localized Aggressive Periodontitis in African American Preadolescent Children.

Purpose: This study aimed to evaluate the potential risk for localized aggressive periodontitis (LAgP) in African American children by detection of the potential periodontal pathogen Aggregatibacter actinomycetemcomitans (Aa) using polymerase chain reaction (PCR) and microbiome analysis.

Methods: Twenty-one pre-adolescents (age range equals 10.7 to 13.

Novel nonsense mutation in MSX1 in familial nonsyndromic oligodontia: subcellular localization and role of homeodomain/MH4.

Nonsyndromic tooth agenesis is one of the most common anomalies in human development. Part of the malformation is inherited and is associated with paired box 9 (PAX9), msh homeobox 1 (MSX1), and axin 2 (AXIN2) mutations. To obtain a comprehensive understanding of the genetic and molecular mechanisms that underlie this genetic disease, we investigated six familial and seven sporadic Japanese cases of nonsyndromic tooth agenesis.

Clinical and functional data implicate the Arg(151)Ser variant of MSX1 in familial hypodontia.

Multiple previous reports confirm that several missense alleles of MSX1 exhibit Mendelian inheritance of an oligodontia phenotype (agenesis of more than six secondary teeth besides third molars). However, the extent to which missense MSX1 alleles contribute to common, multifactorial disorders is less certain. It is still not yet clear whether multiple non-synonomous MSX1-coding variants identified among patients with oral clefting are merely neutral polymorphisms or whether any of these might represent real mutations with mild effects.

Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers.

Background: Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs.

Results: Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades.

Zebrafish Wnt9b synteny and expression during first and second arch, heart, and pectoral fin bud morphogenesis.

Roles for Wnt9b in craniofacial development are indicated by the cleft lip mutant phenotype observed in the A/WySn mouse strain,(1) caused by a retrotransposon insertion mutation at the Wnt9b locus. Analyses of the zebrafish Wnt9b ortholog, wnt9b, were pursued to provide insight into early vertebrate craniofacial patterning events mediated by Wnt9b signaling. Zebrafish wnt9b cDNA clones were isolated and found to encode an open reading frame of 358 amino acids, with 68% amino acid identity to mouse Wnt9b and 70% amino acid identity to human WNT9B.

PVRL1 variants contribute to non-syndromic cleft lip and palate in multiple populations.

Poliovirus Receptor Like-1 (PVRL1) is a member of the immunoglobulin super family that acts in the initiation and maintenance of epithelial adherens junctions and is mutated in the cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1, OMIM #225000). In addition, a common non-sense mutation in PVRL1 was discovered more often among non-syndromic sporadic clefting cases in Northern Venezuela in a previous case-control study. The present work sought to ascertain the role of PVRL1 in the sporadic forms of orofacial clefting in multiple populations.

In a Vietnamese population, MSX1 variants contribute to cleft lip and palate.

Purpose: To identify causes of nonsyndromic cleft lip and palate in a Vietnamese population.

Methods: In this study, 175 families with at least one case of cleft lip and/or palate were studied using the candidate genes TGFA, MSX1, and TGFB3.

Results: Transmission distortion for alleles of MSX1 were demonstrated for the whole population and two missense mutations were identified, including one (P147Q) that is found in approximately 2% of the population.