The genetic factors contributing to the risk of cleft lip-cleft palate and their clinical utility

Askarian, Saeedeh; Gholami, Masoumeh; Khalili-Tanha, Ghazaleh; Tehrani, Negin Chaeichi; Joudi, Marjan; Khazaei, Mojtaba; Ferns, Gordon A.; Hassanian, Seyed Mahdi; Joodi, Marjan

doi:10.1007/s10006-022-01052-3

Cited by 6 publications

(6 citation statements)

References 81 publications

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“…It is known that polygenic nonsyndromic forms of orofacial clefts in humans can be associated with predisposing germinal DNA variants or fetal exposure to teratogenic factors, while syndromic forms can be caused by chromosomal aberrations or single gene mutation [27]. Chromosome analysis is commonly used in studies of congenital malformation.…”

Section: Discussionmentioning

confidence: 99%

Cleft Lip and Palate in Four Full-Sib Puppies from a Single Litter of Staffordshire Bull Terrier Dogs: An Anatomical and Genetic Study

Ruszkowski,

Nowacka-Woszuk,

Nowak

et al. 2023

Animals

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Cleft lip and palate (CLP) is a well-known congenital defect in dogs, characterized by abnormal communication between the oral and nasal cavities. Its incidence rate is high and affects all dog breeds. The etiology of CLP is thought to be multifactorial, caused by both genetic and environmental factors. In this study, four puppies out of seven from a single litter of Staffordshire Bull Terrier dogs with craniofacial abnormalities were anatomically and genetically examined. Classical anatomical preparation, dyed-latex-injection of the arterial vessels, and cone-beam computed tomography were used. The puppies showed variations in their observable abnormalities: three of them had a complete cleft of the palate on both sides, while one puppy had a cleft on the right side only. Cytogenetic analysis showed a normal diploid chromosome number (2n = 78,XX or 78,XY) in the studied animals. Known genomic variants of CLP were examined in the ADAMTS20, DLX6, and MYH3 genes, but no mutations were identified. Further studies are needed to identify the breed-specific genetic variants associated with canine CLP.

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Section: Discussionmentioning

confidence: 99%

Cleft Lip and Palate in Four Full-Sib Puppies from a Single Litter of Staffordshire Bull Terrier Dogs: An Anatomical and Genetic Study

Ruszkowski,

Nowacka-Woszuk,

Nowak

et al. 2023

Animals

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“…Despite the various factors that may cause CLP, medical professionals have developed treatments to address CLP problems that allow patients to live a healthier and better life (Martinelli et al, 2020). Genetic factors have also been reported to contribute to CLP disorders, such as chromosomal abnormalities and family history (Blue, 2012;Askarian, 2022;Ganatra et al, 2021). Certain genetic variants such as TBX22, IRF6, and PVRL1 have also been reported to be associated with CLP risk (Askarian, 2022).…”

Section: Cleft Lip/palatementioning

confidence: 99%

Understanding of Speech Production in Cleft Lip/Palate

Yohana,

Handoko

2024

Arbitrer

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A cleft lip is a disorder caused by the incomplete joining of the lips or palate during fetal development. This condition can result in a variety of physical impairments, speech impairments, and even psychological impairments that can affect a person’s life. Patients with cleft lip usually suffer from dental problems, speech problems, and breathing and hearing problems. This condition can certainly lead to emotional and social problems that require attention from various parties, including surgeons, dentists, speech therapists, and psychologists, essential. Patients with cleft disorders usually have an inability to produce speech sounds due to the insufficient amount of air pressure passing through the oral cavity. The severity of the disorder depends on various factors such as the intensity of the cleft, age at the surgery, and hearing loss. Early support and treatment can greatly improve patients’ quality of life. It is necessary to conduct comprehensive research to address the different issues associated with cleft lip/palate. This involves not only healthcare professionals, such as speech-language pathologists, surgeons, orthodontists, and pediatric dentists, but also communication experts, such as linguists, to develop effective treatments and strategies. This review article discusses the relationship between clefts and speech production, as well as the factors that play a role in improving the quality of life of patients with cleft. The article aims to provide a comprehensive overview of clefts, serving as a reference for dentists, surgeons, linguists, and other professionals who work with cleft patients.

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“…Although the signaling mechanisms for the fusion event are complex and not fully understood, certain signaling components have been revealed as key players and are investigated in this study, including transforming growth factor beta-3 (TGFβ3), bone morphogenetic proteins (BMPs), fibroblast growth factors (FGFs), interferon regulatory factor 6 (IRF6), Rhoassociated coil-coil kinase-1 (ROCK1), GABA receptors and ERK signaling, adhesion molecule E-cadherin, ECM matrix metalloproteinases (MMPs), and microtubule polymerization, usually through the use of mouse models. Many of these components have been confirmed in humans by identifying the genetic anomalies in human subjects with CP (Askarian et al, 2022;Baroni et al, 2006;Bush & Jiang, 2012;Kohli & Kohli, 2012;Reynolds et al, 2020). Mutations in genes IRF6, FGFRs, FGFs, BMP4, ROCK, RAR, and TGFβ3 have been identified as candidates responsible for CP in humans (Askarian et al, 2022;Bush & Jiang, 2012;Dixon et al, 2011;Palmieri et al, 2020;Reynolds et al, 2020;Schutte et al, 1993).…”

Section: Introductionmentioning

confidence: 98%

“…Many of these components have been confirmed in humans by identifying the genetic anomalies in human subjects with CP (Askarian et al, 2022;Baroni et al, 2006;Bush & Jiang, 2012;Kohli & Kohli, 2012;Reynolds et al, 2020). Mutations in genes IRF6, FGFRs, FGFs, BMP4, ROCK, RAR, and TGFβ3 have been identified as candidates responsible for CP in humans (Askarian et al, 2022;Bush & Jiang, 2012;Dixon et al, 2011;Palmieri et al, 2020;Reynolds et al, 2020;Schutte et al, 1993).…”

Section: Introductionmentioning

confidence: 98%

An improved multicellular human organoid model for the study of chemical effects on palatal fusion

Wolf,

Fitzpatrick,

Becker

et al. 2023

Birth Defects Research

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BackgroundTissue fusion is a mechanism involved in the development of the heart, iris, genital tubercle, neural tube, and palate during embryogenesis. Failed fusion of the palatal shelves could result in cleft palate (CP), a common birth defect. Organotypic models constructed of human cells offer an opportunity to investigate developmental processes in the human. Previously, our laboratory developed an organoid model of the human palate that contains human mesenchyme and epithelial progenitor cells to study the effects of chemicals on fusion.MethodsHere, we developed an organoid model more representative of the embryonic palate that includes three cell types: mesenchyme, endothelial, and epithelial cells. We measured fusion by a decrease in epithelial cells at the contact point between the organoids and compared the effects of CP teratogens on fusion and toxicity in the previous and current organoid models. We further tested additional suspect teratogens in our new model.ResultsWe found that the three‐cell‐type model is more sensitive to fusion inhibition by valproic acid and inhibitors of FGF, BMP, and TGFβRI/II. In this new model, we tested other suspect CP teratogens and found that nocodazole, topiramate, and Y27632 inhibit fusion at concentrations that do not induce toxicity.ConclusionThis sensitive human three‐cell‐type organotypic model accurately evaluates chemicals for cleft palate teratogenicity.

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The genetic factors contributing to the risk of cleft lip-cleft palate and their clinical utility

Cited by 6 publications

References 81 publications

Cleft Lip and Palate in Four Full-Sib Puppies from a Single Litter of Staffordshire Bull Terrier Dogs: An Anatomical and Genetic Study

Cleft Lip and Palate in Four Full-Sib Puppies from a Single Litter of Staffordshire Bull Terrier Dogs: An Anatomical and Genetic Study

Understanding of Speech Production in Cleft Lip/Palate

An improved multicellular human organoid model for the study of chemical effects on palatal fusion

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