Journal article
Whole Exome Sequencing Identifies Damaging Variants in Indonesians with Clefts
The Cleft palate-craniofacial journal, Vol.62(3), pp.460-465
03/2025
DOI: 10.1177/10556656231210085
PMID: 37876262
Abstract
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.
Details
- Title: Subtitle
- Whole Exome Sequencing Identifies Damaging Variants in Indonesians with Clefts
- Creators
- Emmanuel Aladenika - University of IowaAni Maskoen - Padjadjaran UniversityWaheed Awotoye - University of IowaRasyid Abdulaziz - Padjadjaran UniversityAzeez Alade - University of IowaSaskia Lenggogeni Nasroen - Padjadjaran UniversityAbimbola Oladayo - University of IowaTamara Busch - University of IowaErli Sarilita - Padjadjaran UniversityAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Cleft palate-craniofacial journal, Vol.62(3), pp.460-465
- DOI
- 10.1177/10556656231210085
- PMID
- 37876262
- NLM abbreviation
- Cleft Palate Craniofac J
- ISSN
- 1055-6656
- eISSN
- 1545-1569
- Publisher
- Sage
- Grant note
- DOI: 10.13039/100000072, name: National Institute of Dental and Craniofacial Research, award: DE28300
- Language
- English
- Electronic publication date
- 10/25/2023
- Date published
- 03/2025
- Academic Unit
- Oral Pathology, Radiology and Medicine; Stead Family Department of Pediatrics; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984502957202771
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