| Objective1.At present,there is no sequencing study on Tessier No.0 cleft with nose deformity.This study intends to use the whole exome sequencing to sequence three pairs of identical twins with Tessier No.0 cleft with nose deformity,in order to find the mutation gene site and analyze the possible pathogenesis.Analyzed the difference between the mRNAs and LncRNAs expression profiles of abnormal epidermal cells and normal epidermal cells in patients with Tessier No.0 cleft with a bifid nose,and screen out the relevant LncRNAs and mRNAs according to the bioinformatics function analysis.2.Tessier No.0 cleft with nose deformity involves hypoplasia of craniomaxillofacial bone and soft tissue.Although its morphological characteristics are mostly caused by dysplasia of soft tissue,understanding the skeletal development of the malformation population will help to further understand the development characteristics of the disease.Three-dimensional CT reconstruction technology was used to measure the skull,explored the mechanism and time of its occurrence and development in coronal,sagittal and angular changes,and understood the relationship between the spatial structure and position changes of each anatomical position.3.At present,there is no recognized surgical method and the best time for Tessier No.0 cleft with nose deformity,and there were only limited case reports.Therefore,we retrospectively analyzed the Tessier No.0 cleft with nose deformity in our center,and proposed our surgical strategies and results.4.Analyzed the facial measurement before and after the operation of Tessier No.0 cleft with nose deformity,and found the gap between patients and ordinary people and the defects of the operation.We also hope that this measurement could show that our surgical method could achieve good aesthetic effect.Methods1.DNA samples from peripheral blood were extracted from three pairs of identical twins and their parents with different phenotypes,and suspicious variant genes were screened out through exon group sequencing and bioinformatics analysis.Sanger sequencing verification was performed after that.In addition,skin samples were collected from 5 patients with stage 2 nasal reconstruction,and LncRNAs and mRNAs were sequenced.The experimental group was nasal deformed skin,and the control group was normal forehead expanded skin.According to the bioinformatics function analysis,the relevant LncRNAs and mRNAs were selected.And based on the intersection of the target genes of the LncRNAs and mRNAs,GO and KEGG analysis were performed,and a PPI network was constructed to predict the Hub genes.2.96 computed tomographic scans were collected from all Tessier No.0 clefts with nose deformity and age-and sex-matched normal people.All patients were divided into five subgroups based on their ages:0 to 6 months,6 months to 2 years,2 to 6 years,6 to 18 years,and over 18 years old.Mimics software was used to analyze and measure the craniometric indexes of the above time periods.3.We analyzed and followed up the patients with Tessier No.0 cleft with nose deformity who had undergone surgery in our hospital from 2012 to 2022,and summarized the surgical methods.4.24 patients who have received multiple surgical treatments in the center and were generally satisfied with the shape of the nose were measured before and after the operation,and the data measurement was analyzed using MB Ruler 4.0 software.Results1.Four suspicious sites were found by whole exon sequencing,but no positive results were obtained after sanger sequencing.According to the determination of mRNA expression profile,4691 differentially expressed mRNAs were finally identified.In addition,according to the determination of LncRNA expression profile,4691 differentially expressed LncRNAs were finally identified.Intersecting the predicted genes of LncRNA target genes and differentially expressed mRNAs,a total of 487 differentially expressed genes were obtained,including 381 upregulated genes and 106 downregulated genes.Ten Hub genes were calculated using Cytoscape software,including TTN,TNNI1,TNNT3,TPM2,TPM1,TPM3,MYH8,MYH3,TMOD3,and MYL3.The TOMD3 gene was the most likely to be associated with malformations,but further validation and functional experiments are needed to prove it.2.The length of the middle and posterior skull base of Tessier No.0 clefts with nose deformity patient was longer than that of the normal people.At the same time,the sphenoid-occipital joint closed earlier,accompanied by upward displacement of the sella turcica.Age subgroup analysis showed that most of the skull base deformities began at 2 years old and mainly affected the development of the nasal bone and the posterior cranial fossa.By analyzing the diameter of nasopharynx and respiratory tract,it was found that its development did not affect the patient’s breathing.3.A total of 33 patients were included in the study.The average age of the patients was 8.79±5.59 years,and the average follow-up time was 5.5 years(5 months to 10 years).For the mild deformity patients,we primarily used local skin flap with silicone or costal cartilage rhinoplasty.With regard to the severe deformity patients,it is difficult to repair local skin flap due to involving multiple nasal subunits.Thus,we adopted nasal reconstruction using an expanded forehead flap for covering with costal cartilage as a framework.During follow-up,28 patients(84.85%)had satisfactory outcomes,four patients(12.12%)had partially satisfactory results,and one patient(3.03%)had an unsatisfactory outcome.4.It was observed that males exhibited a significantly larger nasofrontal angle,and female patients showed a relatively larger nasofacial angle.The medial canthus and nose width index,nasal tip protrusion and nasal width index,and nasal width and ala length index were both significant in males and females.For the method of forehead expansion flap and costal cartilage transplantation,it could better improve the nasal facial angle and is better in shaping the nasal height and less flaring of the alar bases.By comparison,the method of local flaps and silicone prosthesis implantation can better improve the columella length and nasal tip protrusion.ConclusionThrough the morphological analysis of Tessier No.0 cleft with nose deformity patients,it can be seen that the length of the middle and posterior skull base increased during their development,and there may be late closure of the sphenoid-occipital junction and saddle displacement.In addition,we adopted different surgical strategies for patients with different degrees of deformity,which improved the defects of patients to the greatest extent,and the results were also satisfied.The measurement of the face has also improved our understanding of the deformity and the surgical methods.Regrettably,this study failed to find the variant gene locus in the second generations sequencing that led to the inconsistent phenotypes of the three pairs of identical twins with Tessier No.0 cleft with nose deformity.In addition,it was found that the expression of LncRNAs and mRNAs were significantly different between normal skin tissues and abnormal tissues.They may affect the development of face through some signal pathways. |
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