Whole Exome Sequencing Identifies Damaging Variants in Indonesians with Clefts.

OBJECTIVES: The interaction between genomics, genetic and environmental factors have been implicated in non-syndromic orofacial cleft development. In the current study, we investigated the contributions of rare and novel genetic variants in known cleft genes using whole exome sequencing (WES) data of Indonesians with non-syndromic orofacial clefts. DESIGN: WES was conducted on 6 individuals. Variants in their exons were called and annotated. These variants were filtered for novelty and rarity using MAF of 0 and 1%. SETTING: Hospital in Indonesia. PATIENTS/PARTICIPANTS: Indonesians with non-syndromic orofacial clefts. INTERVENTIONS: Deleterious variants were prioritized. Pathogenic amino acid changes effect on protein structure and function were identified using HOPE. MAIN OUTCOME MEASURE(S): Rare and novel variants in known cleft genes were filtered and their deleteriousness were predicted using polyphen, SIFT and CADD. RESULTS: We identified rare (MAF <1%) deleterious variants in 4 craniofacial genes namely MMACHC (rs371937044, MAF = 0.00011). SOS1 (rs190222208, MAF = 0.00045), TULP4 (rs199583035, MAF = 0.067), and MTHFD1L (rs143492706, MAF = 0.0044). MMACHC has a mouse knockout model with facial cleft and failure of palatal fusion. The individual with variant in MMACHC presented with nsCPO. CONCLUSIONS: Our study provides additional evidence for the role of TULP4, SOS1, MTHFD1L and MMACHC genes in nsOFC development. This is the first time MMACHC is implicated in nsOFC development in humans.

A Review on Maternal Parenting, Child's Growth Stunting, and Oral Health.

Stunting has gained global attention as one of the most critical problems in public health. As the first and dominant figure in a child's life, the mother is responsible for determining the proper parenting behaviors to apply to maintain the child's physical health. Stunting is often associated with early childhood caries (ECC) and molar incisor hypomineralization, which can be manifested into each other through various mechanisms. Therefore, it is crucial to explore how far maternal parenting behaviors affect stunting and oral health. This study aims to determine which maternal parenting behaviors can affect stunting and oral health. A systematic search was used through PubMed and Google Scholar to search for published articles between 2011 and 2021. The articles analyze maternal parenting behaviors with stunting and poor oral health. Final analysis was used on 21 articles containing 18 cross-sectional studies, 2 cohort studies, and 1 randomized controlled trial. The result implied that the high prevalence of stunting and ECC is the combined result of prolonged breastfeeding practices (7 articles), poor complementary feeding practice (6 articles), high consumption of sugar (5 articles), and poor oral hygiene practices (5 articles). Maternal parenting styles in the aspect of fulfilling nutrition and maintaining oral health affect the occurrence of stunting and ECC in children.