Functional Effects of SNPs in <i>MYH9</i> and Risks of Nonsyndromic Orofacial Clefts

Wang, Yong; Li, D; Xu, Yuting; Ma, Lan; Lu, Yun; Wang, Z; Wang, Lin; Zhang, W; Pan, Yuqin

doi:10.1177/0022034517743930

Cited by 7 publications

(3 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a previous investigation, our group provided evidence supporting MYH9 as a predisposing factor for CL/P . Its involvement in orofacial clefts, including nsCP, has been confirmed in different populations …”

Section: Introductionmentioning

confidence: 64%

ROCK1 is associated with non‐syndromic cleft palate

Palmieri

Scapoli

Carrozzo

et al. 2019

J Oral Pathology Medicine

View full text Add to dashboard Cite

During human organogenesis, neural crest cells (NCCs), a population of cells with migratory capacity, migrate from the dorsal surface of the neural tube to different regions of the embryo, where they differentiate into a broad range of cell types. 1 In vertebrates, the cranial NCC-derived mesenchyme contributes considerably to the development of the face and pharyngeal arches. 2 Orofacial development is a complex and delicate process, and craniofacial morphogenesis and palate formation occur through a well-orchestrated series of actions-including growth, expansion and fusion of the prominences-which is tightly controlled by the spatial and temporal signalling network. 3 Correct formation of the secondary palate is conditioned by the ability of cells to interact with neighbouring cells Abstract Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. Methods:A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology. K E Y W O R D S association analysis, cleft palate, orofacial malformation, ROCK1 168 |

show abstract

Section: Introductionmentioning

confidence: 64%

ROCK1 is associated with non‐syndromic cleft palate

Palmieri

Scapoli

Carrozzo

et al. 2019

J Oral Pathology Medicine

View full text Add to dashboard Cite

show abstract

“…The odds ratio (OR) and 95% confidence interval (CI) calculated by logistic regression analyses were used to evaluate the association between each SNP and the risk of NSTA. p Value (designated to the association between the SNPs and the risk of TA) < 0.05 but not survive from the Bonferroni correction ( p Bonferroni < 0.0011) was determined as a nominal association (Wang et al, ). HaploReg V2 (https://pubs.broadinstitute.org/mammals/haploreg/haploreg_v2.php) was used to predict regulatory motif alteration.…”

Section: Methodsmentioning

confidence: 99%

Non‐syndromic cleft lip with or without palate susceptible loci is associated with tooth agenesis

et al. 2019

View full text Add to dashboard Cite

Objective Non‐syndromic tooth agenesis (NSTA) may share common genetic factors with non‐syndromic cleft lip with or without cleft palate (NSCL/P). Single‐nucleotide polymorphisms (SNPs) were associated with individual's susceptibility to these anomalies. We selected five NSCL/P‐associated SNPs from our previous genome‐wide association study (GWAS) to test for the associations with NSTA. Materials and methods A total of 677 NSTA cases and 1,144 healthy controls were recruited in this case–control study. Five genome‐wide NSCL/P‐associated SNPs (rs2235371, rs7078160, rs8049367, rs4791774, and rs13041247) were genotyped by TaqMan platform and evaluated for the associations with NSTA using plink software. Results No significant associations between these SNPs and risk of NSTA were observed in the overall analysis and subgroup analysis with the number of missing teeth. However, in the subgroup analysis by tooth position, rs8049367 was nominally associated with mandibular premolar agenesis (Dominant model: ORdom = 0.66, 95% CIdom = 0.47–0.93, pdom = 0.016; Heterozygote model: ORhet = 0.60, 95% CIhet = 0.41–0.88, Phet = 0.008). Rs4791774 showed a nominal association with congenitally missing maxillary canine (Dominant model: ORdom = 0.53, 95% CIdom = 0.28–0.98, pdom = 0.041; Heterozygote model: ORhet = 0.50, 95% CIhet = 0.26–0.97, Phet = 0.041) and premolar (Additive model: OR = 0.59, 95% CI = 0.36–0.96, p = 0.035). Conclusion This study showed that NSCL/P susceptible loci rs8049367 and rs4791774 were probably associated with the risk of NSTA.

show abstract

“…Western blot was performed on the following materials according to a previously described method [38]: HEK293 cells which included an empty vector transfection control, wildtype and mutation-containing plasmids, hMSCs which were transfected by siRNA at day (d) 0 and 14, and zebrafish embryos at 72 hpf and 96 hpf. Primary antibodies were included in Table S4.…”

Section: Western Blotmentioning

confidence: 99%

Skeletal Class III Malocclusion Is Associated with ADAMTS2 Variants and Reduced Expression in a Familial Case

Yao

Zhou

Vona

et al. 2022

IJMS

View full text Add to dashboard Cite

Skeletal Class III malocclusion with maxillary deficiency is a severe maxillofacial disease with unclear pathogenic mechanisms. We recruited a Han Chinese family who was clinically diagnosed with skeletal Class III malocclusion and maxillary deficiency. Using whole exome sequencing, a missense variant in ADAMTS2 (NM_014244: c.3506G>T: p.G1169V) was identified and predicted as deleterious by in silico tools. We also found ADAMTS2 variants associated with deficient maxillary development in a cohort. ADAMTS2 expression in HEK293 cells showed significant decrease due to the variant, which was also consistent in dental pulp stem cells from the proband and a healthy control. In the adamts2-knockdown zebrafish model, the length and width of the ethmoid plate, as well as the length of the palatoquadrate became significantly shorter than the control group (p < 0.001), while there was no significant difference in the length and width of the mandible. The expression of Sox3, which was required in early embryonic craniofacial development, was significantly downregulated in the adamts2-knockdown zebrafish embryos. Bioinformatic and cellular studies showed that the decreased expression of ADAMTS2 may inhibit downstream ErbB signaling pathway transduction and restrain subsequent osteogenesis in human adult mesenchymal stromal cells. Collectively, these data showed that ADAMTS2 (c.3506G>T: p.G1169V) may confer susceptibility to risk of skeletal Class III malocclusion with maxillary deficiency.

show abstract

Functional Effects of SNPs in MYH9 and Risks of Nonsyndromic Orofacial Clefts

Cited by 7 publications

References 27 publications

ROCK1 is associated with non‐syndromic cleft palate

ROCK1 is associated with non‐syndromic cleft palate

Non‐syndromic cleft lip with or without palate susceptible loci is associated with tooth agenesis

Skeletal Class III Malocclusion Is Associated with ADAMTS2 Variants and Reduced Expression in a Familial Case

Contact Info

Product

Resources

About