OBJECTIVE: To explore the genetic basis for a patient with early-onset retinitis pigmentosa (RP). METHODS: A patient who had presented at the West China Hospital of Sichuan University on March 10, 2020 was selected as the study subject. The patient and his parents were subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and in silico analysis. RESULTS: The patient has featured substantial loss of binocular vision field. Funduscopy revealed characteristic bone spicule-type pigment deposits, as well as attenuated retinal arterioles and pale-appearing optic discs. WES revealed that he has harbored compound missense variants of a RP-associated CRB1 gene, including c.2969T>C (p.Leu990Ser) and c.1816T>C (p.Cys606Arg), which were respectively inherited from his father and mother. Homozygous c.1816T>C (p.Cys606Arg) variant has been identified among RP patients, whilst the c.2969T>C (p.Leu990Ser) variant was unreported previously. Both variants were predicted as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The novel compound heterozygous variants of the CRB1 gene probably underlay the early-onset RP in this patient. Above finding has enriched the mutational spectrum of the CRB1 gene.
Male ; Female ; Humans ; China ; Genomics ; Homozygote ; Mothers ; Retinitis Pigmentosa/genetics* ; Eye Proteins/genetics* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with microphthalmia. METHODS: Clinical data of the proband was collected. Whole exome sequencing (WES) was carried out to screen potential pathogenic variants in the proband. Candidate variant was verified by Sanger sequencing of the proband and his family members. Pathogenicity of the variant was predicted by searching the PubMed database and bioinformatic analysis. Sanger sequencing of amniotic fluid sample was carried out for prenatal diagnosis. RESULTS: The proband and his father were found to harbor a heterozygous c.151C>G (p.R51G) variant of the MAB21L2 gene. The same variant was not found in his mother and grandparents. Based on the guidelines of American College of Medical Genetics, the c.151C>G (p.R51G) variant was predicted as likely pathogenic. CONCLUSION The c.151C>G (p.R51G) variant of the MAB21L2 gene probably underlay the microphthalmia in the proband. Above finding has facilitated prenatal diagnosis for this pedigree.
China ; Coloboma ; Eye Proteins ; Female ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics* ; Mutation ; Osteochondrodysplasias ; Pedigree ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with X-linked retinoschisis. METHODS: Clinical data of the pedigree was collected. Following DNA extraction, PCR and Sanger sequencing were carried out to detect potential variant in the RS1 gene. The result was verified by using PCR and restriction fragment length polymorphism assay. RESULTS: All male patients were found to harbor a c.458T>G (p.Val153Gly) variant of the RS1 gene, for which Their mothers were heterozygous carriers. The same variant was not detected among unaffected members of the pedigree as well as 100 healthy controls. Bioinformatic analysis suggested the variant to be pathogenic. CONCLUSION The c.458T>G (p.Val153Gly) variant of the RS1 gene probably underlay the X-linked retinoschisis in this pedigree.
China ; Eye Proteins/genetics* ; Genes, X-Linked ; Humans ; Male ; Mutation ; Pedigree ; Retinoschisis/pathology*

OBJECTIVE: To analyze the correlation of methylation status of dachshund homolog 1 (DACH1) gene in tumor tissues with clinicopathological characteristics and prognosis of patients of esophageal cancer. METHODS: Tumor tissue, paracancerous tissue and normal esophageal mucosal specimens of 104 patients with esophageal cancer were collected. Methylation-specific PCR was used to determine the methylation status of the DACH1 gene. Univariate analysis and multivariate Logistic regression model were used to analyze the correlation between DACH1 methylation status and clinical pathological characteristics of the patients. Kaplan-Meier survival curve was used to analyze the relationship between DACH1 methylation status and prognostic survival of patients. RESULTS: The methylation rate of the DACH1 gene in esophageal cancer tumor tissue was 30.77% (32/104), which was higher than those in adjacent tissues (1.92%) and normal esophageal mucosa (0%) (P< 0.05). The methylation status of the DACH1gene in tumor tissues of patients did not correlate with the patient's age, gender, and pathological type (P> 0.05) but tumor differentiation, TNM staging, and lymph node metastasis(P< 0.05). The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. By March 2020, 89 of the 104 patients had died. Among them, the median survival foresophageal cancer patients with DACH1 gene methylation was 22 months, which was lower than 34 months of those without DACH1 methylation (P< 0.05). CONCLUSION Methylation of the DACH1 gene may be involved in the occurrence and progress of esophageal cancer. The degree of tumor differentiation, TNM stage, and lymph node metastasis of patients are independent risk factors for the methylation status of the DACH1 gene. Patients with esophageal cancer but unmethylated DACH1 gene have a longer prognostic survival.
Esophageal Neoplasms/pathology* ; Eye Proteins/genetics* ; Humans ; Lymphatic Metastasis ; Methylation ; Neoplasm Staging ; Prognosis ; Transcription Factors

BACKGROUND: The anti-tumor effect of pigment epithelium-derived factor (PEDF) has been widely confirmed. However, the anti-tumor effect of its peptides is rarely reported. This study aims to investigate the effects of PEDF and its peptides on the apoptosis and migration of non-small cell lung cancer (NSCLC). METHODS: In this study, A549 cells and H1299 cells were selected as the research object, and the cells were divided into normal group, PEDF treatment group, 34 peptide treatment group, 44 peptide treatment group and 34+44 peptide treatment group by administering different drugs at the same concentration to the cells. The proliferation activity of cells in each group was detected by CCK-8 method; the migration ability of cells was detected by scratch test; the expression levels of apoptosis related proteins such as protein kinase 3 (RIP3) and cleaved-caspase-3 were detected by Western blot; the expression levels of epithelial mesenchymal transition (EMT) markers in each group, such as cadherin (E-cadherin) and α-smooth muscle actin (α-SMA) were detected by Western blot; the apoptosis rate of each group was detected by flow cytometry. RESULTS: The results of CCK-8 showed that PEDF and its peptides could inhibit cell proliferation, and the inhibitory effect of 34+44 peptide was the strongest (P<0.05); Observation under the microscope found that PEDF and its peptides can inhibit the proliferation and mesenchymal transformation of A549 cells and H1299 cells, and the inhibitory effect of the 34+44 peptide group is the most obvious; Western blot indicated that compared with other groups, the expressions of cleaved-caspase-3 and RIP3 in 34+44 peptide group were significantly higher (P<0.05), and the expressions of EMT protein E-cadherin were higher, the expression of α-SMA decreased (P<0.05); The results of flow cytometry showed that the apoptosis rate of 34+44 peptide group was significantly higher than those of other groups (P<0.05); The scratch test showed that compared with all the other groups, the healing rate of 34+44 peptide group was the lowest (P<0.05). CONCLUSIONS 34+44 combination peptide can better promote the apoptosis of NSCLC, inhibit the migration of NSCLC, and thereby inhibit the growth of NSCLC.
Apoptosis ; Cadherins/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Caspase 3 ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Eye Proteins ; Humans ; Lung Neoplasms/genetics* ; Nerve Growth Factors ; Peptides/pharmacology* ; Serpins ; Sincalide

OBJECTIVE: To identify pathogenic variants in two families with patients suspected for Joubert syndrome(UBST) by cerebellar vermis hypoplasia. METHODS: Clinical data and peripheral venous blood and skin tissue samples were collected for the extraction of genomic DNA. Potential variants were screened by using targeted capture and next generation sequencing. Suspected variants were validated by PCR and Sanger sequencing. The frequency of the variants in the population was calculated. Pathogenicity of the variants was predicted by following the guidelines of the American College of Medical Genetics and Genomics (ACMG). Prenatal diagnosis was provided to these families upon subsequent pregnancy. RESULTS: The proband of family 1 was found to harbor homozygous c.2072delT (p.F691S*fs19) frameshift variant of the AHI1 gene, which may cause premature termination of translation of the Abelson helper integration site 1 after the 691st amino acid. The proband of family 2 was found to harbor compound heterozygous variants of the CPLANE1 gene, namely c.7243dupA (p.T2415Nfs*7) and c.8001delG (p.K2667Nfs*31), which can respectively lead to premature termination of translation of ciliogenesis and planar polarity effector 1 after the 2145th and 2667th amino acids. All of the three variants were previously unreported, and were predicted to be pathogenic by bioinformatic analysis. CONCLUSION The AHI1 c.2072delT and CPLANE1 c.7243dupA and c.8001delG variants probably underlay JBTS3 in family 1 and JBTS17 in family 2, respectively. Based on above results, prenatal diagnosis may be offered to the affected families upon their subsequent pregnancies.
Abnormalities, Multiple ; diagnosis ; genetics ; Adaptor Proteins, Vesicular Transport ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pregnancy ; Prenatal Diagnosis ; Retina ; abnormalities

OBJECTIVE: To identify the pathogenic mutation underlying retinitis pigmentosa in a large pedigree. METHODS: The pedigree has included three generations showing an autosomal dominant transmission of retinitis pigmentosa. Potential mutations were screened using a retinitis pigmentosa gene panel and an Ion PGM platform. Suspected mutation was verified by Sanger sequencing. RESULTS: A novel heterozygous missense mutation, c.251T>C(p.Leu84Pro), was identified in the RHO gene. The mutation has co-segregated with the retinitis pigmentosa phenotype among all family members and was not found in public databases ExAC, 1000G and dbSNP or 831 healthy controls. The mutation was predicted to be damaging by three major protein-predicting software. CONCLUSION The c.251T>C (p.Leu84Pro) mutation of the RHO gene is a novel pathogenic mutation underlying the retinitis pigmentosa phenotype in this pedigree. Above findings have enabled prenatal diagnosis for the pedigree.
DNA Mutational Analysis ; Eye Proteins ; Humans ; Mutation ; Mutation, Missense ; Pedigree ; Phenotype ; Retinitis Pigmentosa ; genetics

OBJECTIVE: To explore the pathogenesis of two fetuses from one family affected with Joubert syndrome (JS). METHODS: Whole exome sequencing was employed to screen potential mutations in both fetuses. Suspected mutations were verified by Sanger sequencing. Impact of intronic mutations on DNA transcription was validated by cDNA analysis. RESULTS: Two novel TCTN1 mutations, c.342-8A>G and c.1494+1G>A, were identified in exons 2 and 12, respectively.cDNA analysis confirmed the pathogenic nature of both mutations with interference of normal splicing resulting in production of truncated proteins. CONCLUSION The genetic etiology of the family affected with JS has been identified.Above findings have enriched the mutation spectrum of TCTN1gene and facilitated understanding of the genotype-phenotype correlation of JS.
Abnormalities, Multiple ; diagnosis ; genetics ; Cerebellum ; abnormalities ; Eye Abnormalities ; diagnosis ; genetics ; Humans ; Kidney Diseases, Cystic ; diagnosis ; genetics ; Membrane Proteins ; genetics ; Mutation ; Pedigree ; Retina ; abnormalities ; Whole Exome Sequencing

OBJECTIVE: To screen for MYOC gene variants among sporadic patients with primary open angle glaucoma (POAG). METHODS: For 398 patients with POAG, Sanger sequencing was applied to detect potential variants of the MYOC gene. RESULTS: Eight patients (2.0%) were found to harbor variations of the MYOC gene. These included five types of variants, among which c.667C>T (p.Pro223Ser) and c.1138G>T (p.Asp380Tyr) were novel. c.382C>T (p.Arg128Trp), c.1109C>T(p.Pro370Leu) and c.1130C>A (p.Thr377Lys) were previously associated with POAG. Alignment of amino acid sequences of MYOC proteins of various species revealed that the two novel variants have occurred at highly conserved positions. c.1138G>T was predicted to be possible pathogenic by Bioinformatic analysis. CONCLUSION Two novel variants of the MYOC gene were detected among sporadic POAG patients, which enriched its variant spectrum.
Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Mutation

OBJECTIVETo explore the genetic etiology of a pedigree affected with hereditary retinitis pigmentosa.

METHODSHigh-throughput DNA sequencing was used to analyze the sequences of 173 genes associated with hereditary eye diseases in the proband. Suspected mutation was verified with PCR amplification and Sanger sequencing.

RESULTSThe proband was found to have carried a c.570_571 ins GAAGATGCTGT insertional mutation in the RP2 gene located on the X chromosome. All female carriers of the pedigree were heterozygous, while all affected males were hemizygous for the same mutation.

CONCLUSIONThe inheritance pattern of this retinitis pigmentosa pedigree was X-linked recessive. The c.570_571 ins GAAGATGCTGT insertional mutation of the RP2 gene probably underlies the disease.

Eye Proteins ; genetics ; Female ; Genetic Diseases, X-Linked ; genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Membrane Proteins ; genetics ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Retinitis Pigmentosa ; genetics