OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with non-syndromic hearing loss (NSHL). METHODS: Commercialized gene chip was applied to detect common mutations associated with congenital deafness. Whole exome sequencing was carried out for patients for whom gene chip yielded a negative result. Candidate variants were verified by Sanger sequencing. RESULTS: Two patients from the pedigree were discovered to carry compound heterozygous variants of the TRIOBP gene, namely c.3299C>A and c.5185-2A>G. Their parents had normal hearing and were both heterozygous carriers of the above variants. Both variants had co-segregated with the disease phenotype in the pedigree and were unreported previously. CONCLUSION Pathogenic variants of the TRIOBP gene comprise an important factor for NSHL. The novel c.5185-2A>G and c.3299C>A variants discovered in this study have enriched the mutational spectrum of the TRIOBP gene and enabled molecular diagnosis and genetic counseling for the family.
Deafness/genetics* ; Hearing Loss, Sensorineural/genetics* ; Heterozygote ; Humans ; Microfilament Proteins/genetics* ; Mutation ; Pedigree ; Whole Exome Sequencing

Adolescent ; Adult ; Female ; Fibrillins ; Humans ; Male ; Marfan Syndrome ; diagnosis ; genetics ; Microfilament Proteins ; genetics ; Young Adult

Animals ; Cardiovascular Diseases ; genetics ; pathology ; Cell Proliferation ; Genes ; Microfilament Proteins ; genetics ; Muscle Proteins ; genetics ; Muscle, Smooth, Vascular ; pathology ; Rats

OBJECTIVETo identify the mayven-interacting proteins and study the effect of mayven on multiple sclerosis pathogenesis.

METHODSThe full length and four different fragments of mayven gene were amplified by polymerase chain reaction (PCR) with specific primers and were cloned into the yeast expression vector pDBLeu. Then, the recombinant plasmids were transformed into MAV203 yeast strain. The autonomous activation of their expression products was detected.

RESULTSThe yeast expression vectors of mayven, which include a full-length and four different fragments, were constructed successfully. Full length P1, fragments P3 and P4 have no effect on the expression of HIS3 and LacZ gene, but fragments P7 and P8 do. The C-terminal of Mayven gene may contain a transcription activation domain.

CONCLUSIONFull length P1, fragments P3 and P4 of the mayven gene can be used to screen the mayven-interacting proteins, but whether Mayven has transcriptional activation activity need to be studied.

Microfilament Proteins ; genetics ; Models, Genetic ; Multiple Sclerosis ; genetics ; Nerve Tissue Proteins ; genetics ; Polymerase Chain Reaction ; Two-Hybrid System Techniques

To understand the function of Mayven and investigate the pathogenesis of multiple sclerosis, the gene sequences of different truncated Mayven were amplified from the gene library of human brain. These truncated fragments, including fragment P1 (1-902 bp), fragment P2 (1-523 bp), fragment P3 (507-182 bp) and fragment P4 (887-1782 bp), were cloned into pGEX-4T-2 vector to construct recombinant plasmids. The recombinant plasmids were transformed into E. coli BL21(DE3) and induced to express by IPTG. The expressed proteins were detected by SDS-PAGE and Western blot, and were purified by GST purifying system. The results showed that recombinant express vectors of different truncated GST-Mayven were successfully constructed and were expressed in soluble form protein induced by IPTG. The fusion proteins have good reactivity to GST antibody. The construction of recombinant express vectors of different truncated GST-Mayven lays a basis for further function study on Mayven.
Escherichia coli ; genetics ; metabolism ; Genetic Vectors ; Humans ; Microfilament Proteins ; genetics ; metabolism ; Multiple Sclerosis ; genetics ; Nerve Tissue Proteins ; genetics ; metabolism ; Recombinant Fusion Proteins ; genetics ; metabolism

BACKGROUNDMutations in the fibrillin-1 gene have been identified in patients with Marfan syndrome (MFS). This study aimed to identify the molecular defects in the fibrillin-1 gene in a Chinese family with Marfan syndrome, accompanied by aortic aneurysms/dissection.

METHODSTwo patients and one non-carrier in the family underwent complete physical, ophthalmic, and cardiovascular examinations. Genomic DNA was extracted from leukocytes of venous blood of these individuals in the family as well as 50 healthy normal controls. Polymerase chain reaction amplification and direct sequencing of all 65 coding exons of fibrillin-1 gene were analyzed.

RESULTSWe found a novel mutation (c.8547T > G, p.Tyr2849X) in exon 65 of fibrillin-1 gene in a Chinese proband with Marfan syndrome, accompanied by aortic aneurysms/dissection. Sudden death at a young age of affected members was seen due to aortic aneurysms/dissection. By evaluating genotype-phenotype correlations of patients with mutations in the 3' end of fibrillin-1 gene (exons 64 and 65), we also found that the presence of nonsense mutations occurring in exons 64 and 65 appeared to be an indicator of early-onset aortic risk and sudden death.

CONCLUSIONSThese results expand the mutation spectrum of fibrillin-1 gene and help in the study of the molecular pathogenesis of Marfan syndrome, indicating that mutations occurring in the 3' end of fibrillin-1 gene may play an independent functional role in the pathogenesis of Marfan syndrome.

Adult ; Female ; Fibrillin-1 ; Fibrillins ; Genotype ; Humans ; Male ; Marfan Syndrome ; etiology ; genetics ; Microfilament Proteins ; genetics ; Middle Aged ; Mutation ; Phenotype

OBJECTIVESTo analyze the FBN1 mutations in Chinese patients with Marfan syndrome (MFS) and to make a genetic diagnosis based on haplotype linkage analysis for MFS.

METHODSNine MFS families (17 patients) were analyzed with single strand conformation polymorphism (SSCP) and sequencing. Four primers were designed for the flanking sequences of FBN1 gene and used for haplotype-segregation analysis of MFS(B).

RESULTSSSCP band alteration was detected in the PCR products for exon 25 in MFS(A) II:1. Direct sequencing revealed a small 13 bp deletion; the deleted sequence is gccTc Tgcaccca at bases 3243-3456 of the cDNA in exon 25. This mutation was novel. MFS(B) families were analyzed using the haplotype linkage technique. The data suggested that MFS(B) families were linked to the FBN1 gene. The proband's daughter was an asymptomatic patient.

CONCLUSIONThe combination of mutation detection and chromosome haplotype analysis can provide better evidence for a genetic diagnosis of MFS.

Fibrillin-1 ; Fibrillins ; Genetic Linkage ; Haplotypes ; Humans ; Marfan Syndrome ; diagnosis ; genetics ; Microfilament Proteins ; genetics ; Mutation ; Polymorphism, Single-Stranded Conformational

OBJECTIVE: To investigate the expression of Calponin-1 and Transgenlin in the uterine smooth muscles during normal labor on-sets, and to evaluate their effect on initiating the normal labor. METHODS: A total of 14 uterine bodies and lower segments of human pregnancy were divided to a non-labor group (NIL) and a labor group(IL). Immunohistochemical technology and Western blot were used to determine the expression of Calponin-1 and Transgelin in the 2 groups. RESULTS: Immunohistochemical detection and Western blot showed that Calponin-1 protein in the uterine smooth muscle tissue of the body and the lower uterine segment of smooth muscle tissues had significant difference (P<0.05). The expression of Transgelin in the uterine body smooth muscle tissue in the IL was higher than that in the NIL(P<0.05). In the lower uterine segments of the smooth muscle, the expression of Transgelin was not significantly different in the 2 groups (P>0.05). CONCLUSION Calponin-1 of the uterine smooth muscle and Transgelin of the uterine body smooth muscle may involve in the regulation of uterine smooth muscle contractility, which is closely related to child birth launch.
Adult ; Calcium-Binding Proteins ; genetics ; metabolism ; Female ; Humans ; Labor Onset ; metabolism ; Microfilament Proteins ; genetics ; metabolism ; Muscle Proteins ; genetics ; metabolism ; Myometrium ; metabolism ; Pregnancy ; Uterine Contraction ; metabolism

No abstract available.
Child, Preschool ; DNA Mutational Analysis ; Diseases in Twins/*genetics/metabolism ; Ectopia Lentis/*genetics/metabolism ; Extracellular Matrix Proteins ; Humans ; Male ; Microfilament Proteins/*genetics/metabolism ; *Mutation ; *Twins, Monozygotic

Marfan syndrome (MFS) is a potentially fatal connective disorder that is inherited as an autosomal dominant trait with a prevalence of around 2-3 in 10000 live births. It is characterized by defects in the cardiovascular, skeletal and ocular systems. Evidence from genetic indicates that mutations in FBN1, the gene that encodes fibrillin-1 are responsible for MFS. In addition to skeletal, ocular, and cardiovascular feathers, patients with MFS have also involvement of skin, integument, lungs, and muscle tissue, and the condition in sudden death is also very common due to severe abnormalities of cardiovascular system.
Cardiovascular Diseases/pathology* ; Eye Diseases/pathology* ; Genotype ; Humans ; Marfan Syndrome/pathology* ; Microfilament Proteins/genetics* ; Musculoskeletal Diseases/pathology* ; Mutation ; Phenotype