Identification of a novel mutation of Platelet-Derived Growth Factor-C (PDGFC) gene in a girl with Non-Syndromic cleft lip and palate

• Published in: Gene 2024-06, Vol.910, p.148335-148335, Article 148335
• Main Authors: Rahnama, Maryam, Movahedi, Tahereh, Eslahi, Atieh, Kaseb-Mojaver, Nasrin, Alerasool, Masoome, Adabi, Nasim, Mojarrad, Majid
• Format: Article
• Language: English
• Subjects: Animals; Child, Preschool; Cleft lip; Cleft Lip - genetics; Cleft lip with/without cleft palate; Cleft palate; Cleft Palate - genetics; Female; Humans; Iran; Mutation; Platelet-Derived Growth Factor - genetics; platelet-derived growth factor C
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2024.148335

•1. This study unveils a previously unreported frameshift mutation (c.546dupA, p.L183fs) in the Platelet-Derived Growth Factor-C (PDGFC) gene, shedding light on a potential genetic factor linked to cleft lip and palate (CL/CP).•2. Building on prior research identifying candidate loci for CL/CP, this work adds to the understanding of the genetic landscape by pinpointing a mutation in the PDGFC gene, a critical player in embryogenesis during the induction of neural crest cells.•3. Through the case presentation of a 3-year-old girl with non-syndromic CL/CP and a family history of craniofacial clefts, this study underscores the importance of genetic analysis, revealing the homozygous c.546dupA mutation in the PDGFC gene as a potential causative factor.•4. The identified c.546dupA mutation is not documented in human genome databases, emphasizing its novelty and suggesting a potential rare genetic variant associated with non-syndromic CL/CP.•5. Sanger sequencing confirms the parents as carriers of the identified mutation, highlighting the importance of genetic counseling in understanding the inheritance pattern and informing future reproductive decisions.•6. The study prompts further investigations into the specific pathogenesis of the PDGFC mutation in non-syndromic CL/CP, providing a foundation for future studies aimed at unraveling the underlying molecular mechanisms.•7. The identification of the mutation in an Iranian family underscores the importance of population-specific genetic studies, acknowledging potential variations in the genetic basis of CL/CP across diverse populations.•8. The study concludes by emphasizing the need for additional research to delve deeper into the functional implications of the PDGFC mutation and its role in the manifestation of non-syndromic CL/CP, paving the way for targeted therapeutic interventions and genetic counseling strategies. Cleft lip with or without cleft palate (CL/CP) is a prevalent congenital malformation. Approximately 16 candidate loci for CL/CP have been identified in both animal models and humans through association or genetic linkage studies. One of these loci is the platelet-derived growth factor-C (PDGFC) gene. In animal models, a mutation in the PDGFC gene has been shown to lead to CL/CP, with PDGF-C protein serving as a growth factor for mesenchymal cells, playing a crucial role in embryogenesis during the induction of neural crest cells. In this study, we present the identification of a novel frameshift