Mutation Screening for Molecular Pathogenicity of MSX1 gene in Human Cleft lip Subjects from Khyber Pakhtunkhwa

Abstract

Background: Cleft lip palate is a genetically heterogeneous group of diseases. Cleft lip-palate can cause deleterious effects during growth on the appearance, language and hearing abilities. Multidisciplinary approach to the care for children born with these defects is required.
Objective: To investigate a selected MSX1gene for the molecular pathogenicity in the two families of cleft lip and palate segregating disease phenotype in autosomal recessive fashion.
Material and Methods: After getting informed written consent and approved from the Institutional Review Board, KMU Peshawar, clinical Investigations of the selected two families were performed in the HMC, Peshawar. Blood Sampling was done in EDTA tubes and DNA was extruded through standard procedure. PCR was performed. Primers were designed using Primers 3 Software and DNA Sequencing done. Sequencing was performed. Bioedit Software and ClustalW were used for Sequence Alignment. Mutation analysis of the pathogenic variant in families A and B demonstrating autosomal recessive non-syndromic cleft lip palate phenotype was performed.
Results: while analyzing bidirectional sequencing of MSX1 gene including all coding exons and intron-exons boundaries in two affected individuals of family A and an affected individual of family B, the affected individuals in each family did not reveal any pathogenic variant. Thus pathogenicity of MSX1 gene in the patients of families A and B exhibiting autosomal recessive non-syndromic cleft lip palate phenotype was excluded.
Conclusion: Mutations screening for molecular pathogenicity of MSX1 gene in affected individuals of families with cleft lip palate phenotypes were investigated and revealed that MSX1gene is not the culprit pathogenic variant in the two families understudy.
Keywords: Autosomal recessive, Heterogeneous group, Non-syndromic, Pathogenic variants, Phenotype,