OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with hereditary dentinogenesis imperfecta (DGI) type II. METHODS: Clinical data of the pedigree members were collected. Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing. RESULTS: Clinical characteristics of the affected family members have included amber teeth along with significant attrition, constricted roots and dentine hypertrophy leading to pulpal obliteration, which were suggestive of DGI type II. All of the affected members were found to have harbored a novel heterozygous c.2837delA (p.Asp946Valfs*368) variant of the DSPP gene which was predicted to be likely pathogenic. CONCLUSION The c.2837delA variant of the DSPP gene probably underlay the disease in this pedigree. Above finding has expanded the variant spectrum of DSPP gene and provided a basis for molecular diagnosis and genetic counseling for this pedigree.
Dentinogenesis Imperfecta/genetics* ; Extracellular Matrix Proteins/genetics* ; Humans ; Mutation ; Pedigree ; Phosphoproteins/genetics* ; Sialoglycoproteins/genetics*

Phosphoproteome is the whole complement of phosphorylated proteins in a cell, tissue or organism, and has become an interesting study subject since the discovery of phosphorylation as a key regulatory mechanism of cell life. Phosphoproteomics is a method which studies the compact of the phosphorylated proteins, expression and modification, interaction and association, rule of the regulatory and so on. Recently, phosphoproteomics is widely used in cancer research. It will provide important information in cancer research, cancer diagnosis, and therapy.
ErbB Receptors ; genetics ; Humans ; Neoplasms ; genetics ; metabolism ; Phosphoproteins ; genetics ; metabolism ; Phosphorylation ; Proteomics ; methods ; Signal Transduction

Objective:By analyzing the clinical phenotypic characteristics and gene sequences of two patients with Treacher Collins syndrome（TCS）, the biological causes of the disease were determined. Then discuss the therapeutic effect of hearing intervention after bone bridge implantation. Methods:All clinical data of the two family members were collected, and the patients signed the informed consent. The peripheral blood of the proband and family members was extracted, DNA was extracted for whole exome sequencing, and Sanger sequencing was performed on the family members for the mutation site.TCOF1genetic mutations analysis was performed on the paitents. Then, the hearing threshold and speech recognition rate of family 2 proband were evaluated and compared under the sound field between bare ear and wearing bone bridge. Results:In the two pedigrees, the probands of both families presented with auricle deformity, zygomatic and mandibular hypoplasia, micrognathia, hypotropia of the eye fissure, and hypoplasia of the medial eyelashes. The proband of Family 1 also presents with specific features including right-sided narrow anterior nasal aperture and dental hypoplasia, which were consistent with the clinical diagnosis of Treacher Collins syndrome. Genetic testing was conducted on both families, and two heterozygous mutations were identified in the TCOF1 gene: c. 1350_1351dupGG（p. A451Gfs*43） and c. 4362_4366del（p. K1457Efs*12）, resulting in frameshift mutations in the amino acid sequence. Sanger sequencing validation of the TCOF1 gene in the parents of the proband in Family 1 did not detect any mutations. Proband 1 TCOF1 c. 1350_1351dupGG heterozygous variants have not been reported previously. The postoperative monosyllabic speech recognition rate of family 2 proband was 76%, the Categories of Auditory Performance（CAP） score was 6, and the Speech Intelligibility Rating（SIR） score was 4. Assessment using the Meaningful Auditory Integration Scale（MAIS） showed notable improvement in the patient's auditory perception, comprehension, and usage of hearing aids. Evaluation using the Glasgow Children's Benefit Inventory and quality of life assessment revealed significant improvements in the child's self care abilities, daily living and learning, social interactions, and psychological well being, as perceived by the parents. Conclusion:This study has elucidated the biological cause of Treacher Collins syndrome, enriched the spectrum of TCOF1 gene mutations in the Chinese population, and demonstrated that bone bridge implantation can improve the auditory and speech recognition rates in TCS patients.
Child ; Humans ; Mandibulofacial Dysostosis/genetics* ; Quality of Life ; Speech ; Parents ; Mutation ; Nuclear Proteins/genetics* ; Phosphoproteins/genetics*

The classification as well as the clinical manifestations of hereditary malformations of dentin are of great concern and have been deeply elucidated. The understanding of its genetic basis also increases progressively. Dentin sialophosphoprotein (DSPP) is the pathogenic gene of dentinogenesis imperfecta type Ⅱ, dentinogenesis imperfecta type Ⅲ and dentin dysplasia type Ⅱ. In this article, the classification of DSPP mutations as well as the resultant dysfunction of the mutant DSPP are summarized respectively and the corresponding clinical manifestations are analyzed. This work will provide a reference for the diagnosis and treatment of hereditary malformations of dentin.
Humans ; Dentinogenesis Imperfecta/pathology* ; Mutation ; Extracellular Matrix Proteins/genetics* ; Phosphoproteins/genetics* ; Sialoglycoproteins/genetics* ; Dentin/pathology*

OBJECTIVETo examine the expression patterns of short palate, lung and nasal epithelium clone 1 (SPLUNC1) gene in human tissues.

METHODSIn situ hybridization was used to detect the expression of SPLUNC1 gene in 37 different human tissues.

RESULTSWe found that SPLUNC1 gene was not expressed in squamous epithelial cells of the palate, epidermis, esophagus, or the esophagus-cardia junction, metaplastic squamous cells in the nasopharynx, trachea, or uterus cervix, or tumor cells of esophageal squamous cell carcinoma or lung squamous cell carcinoma. SPLUNC1 gene was not expressed in the single layer columnar epithelia cells in the stomach, gallbladder, jejunum, colon, endometrium, or uterus cervix. SPLUNC1 expression was detected mainly in pseudostratified columnar epithelial cells in the nasopharynx, trachea and bronchi, and was gradually down-regulated from the upper to lower end of the respiratory tract, but was not detected in the lung tissues. SPLUNC1 expression was detected not only in the duct and serous gland cells in the parotid and submandibular glands, but also in cells of submucosal serous glands in the nasopharynx and lung, but not in the cells of the mucosal glands. The parietal cells of the gastric submucosa and epithelial cells of the lobula and ducts of the mammary glands expressed SPLUNC1. The adenocarcinoma cells in the lung, stomach, colon, mammary gland, uterus endometrium and cervix showed strong expressions of SPLUNC1 gene.

CONCLUSIONSPLUNC1 expression is highly cell-specific in association with the cell functions.

Epithelial Cells ; metabolism ; Gene Expression ; Glycoproteins ; genetics ; metabolism ; Humans ; Organ Specificity ; Phosphoproteins ; genetics ; metabolism

Pleckstrin homology like domain family A member 1(PHLDA1) is also known as T-cell death-associated gene 51 (TDAG51).Studies have demonstrated that the abnormal expression of PHLDA1 is closely associated with the formation,development,and metastasis of tumors.We summarized the latest research advances in the structure and biological properties of PHLDA1,as well as the roles of PHLDA1 in multiple malignanttumors such as breast cancer,cancer,liver gastric cancer,liver cancer,melanoma,and osteosarcoma,aiming to comprehensively reveal the significance of PHLDA1 in the clinical diagnosis of tumors.
Humans ; Female ; Transcription Factors/genetics* ; Phosphoproteins ; Blood Proteins ; Breast Neoplasms/genetics*

Treacher Collins syndrome is a congenital craniofacial malformation with autosomal dominant inheritance as the main genetic pattern. In this condition, the biosynthesis of ribosomes in neural crest cells and neuroepithelial cells is blocked and the number of neural crest cells that migrate to the craniofacial region decreases, causing first and second branchial arch dysplasia. Definite causative genes include treacle ribosome biogenesis factor 1 (tcof1), RNA polymerase Ⅰ and Ⅲ subunit C (polr1c), and RNA polymerase Ⅰ and Ⅲ subunit D (polr1d). This paper provides a review of research of three major patho-genic genes, pathogenesis, phenotypic research, prevention, and treatment of the syndrome.
DNA-Directed RNA Polymerases ; genetics ; Humans ; Mandibulofacial Dysostosis ; genetics ; Neural Crest ; Nuclear Proteins ; Phosphoproteins

Treacher Collins syndrome (TCS, OMIM 154500), also known as Franceschetti-Klein syndrome, is a rare disorder that affects the first and second branchial arches. The estimated incidence is 1/50 000 live births. Mutations in TCOF1 (78%-93%) and POLR1C or POLR1D (8%) cause the disease. Most of TCS cases are inherited in a dominant pattern, while a small proportion are inherited in a recessive pattern. TCS has a variable phenotype with typical clinical characteristics including downward-slant of palpebral fissure, malar hypoplasia, mandibular hypoplasia and microtia. TCS management is a multidisciplinary affair, as interventions range from reconstructive to psychosocial. For hearing rehabilitation, TCS patients may have the choices of BAHA, ponto, vibrant soundbridge or bonebridge implantation. In this review, we summarize the TCS clinical malformations, diagnosis, genetics, management and auditory rehabilitation.
DNA-Directed RNA Polymerases ; genetics ; Facial Bones ; abnormalities ; Humans ; Mandibulofacial Dysostosis ; diagnosis ; genetics ; rehabilitation ; Mutation ; Nuclear Proteins ; genetics ; Phosphoproteins ; genetics

Oncogene StarD4 had the function of promoting proliferation and metastasis of triple-negative breast cancer (TNBC), but its clinical value and molecular mechanism are unknown. This paper found that StarD4 was highly expressed in cancer tissues of TNBC patients, and higher expression level of StarD4 in TNBC patient resulted in poorer prognosis. Based on transcriptomics of MDA-MB-231 cell model, the results of bioinformatics analysis showed that down-regulated expression level of StarD4 led to overall downregulation of cholesterol-relative genes and significant enrichment of cancer mechanism and pathway. Further analysis and investigation verified that StarD4 might cross-promote the protein stability of receptor ITGA5 through the cholesterol pathway to enhance TNBC progression, which provides guidance for clinical application of TNBC diagnosis and treatment.
Breast Neoplasms/genetics* ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Lipids ; Membrane Transport Proteins ; Phosphoproteins

OBJECTIVETo determine AF172993 sequence is either the complete CDS or a transcript variant.

METHODSRT-PCR was used to amplify the CDS sequence of Plunc, which was subsequently cloned into the pEGFP-N1 eukaryotic expression vector. After bi-directional sequence analysis, the sequence obtained was blasted against the AF172993 sequence, nr database and human genome database.

RESULTSIn CDS of the new cloned sequence, the 658 base A in the AF172993 sequence was replaced by C, and the corresponding genetic code was also converted from AAG to CAG, leading to the alteration of the amino acid Gln to Lys. In addition, the base C at the 658 position of the CDS showed perfect match with the base C at 2094188 position in human chromosome 20.

CONCLUSIONThe base A at the 658 position of AF172993 sequence of Plunc is a mutation site, which alters the coding of the amino acid. AF172993 sequence is actually a transcript variant of Plunc, and the annotation to AF172993 in GenBank database is not correct and need to be revised.

Cloning, Molecular ; Databases, Nucleic Acid ; Glycoproteins ; genetics ; Humans ; Mutation, Missense ; Open Reading Frames ; genetics ; Phosphoproteins ; genetics ; Sequence Analysis, DNA