Spondyloepiphyseal dysplasia(SED) includes a group of disorders that cause deformation of vertebrae and epiphyses following gene mutations.Its main clinical manifestations are short stature(with a disproportionately short-trunk),chest malformation and early-onset joint degeneration.These disorders are broadly categorized into two subtypes: congenita(SEDC) and tarda(SEDT).In the 2006 revision of the International Nosology and Classification of Genetic Skeletal Disorders,372 different conditions were listed,of which 215 were associated with one or more of 140 different genes.SEDC has consistently been shown to correlate with defects in the gene COL2A1 on the long arm of chromosome 12,whose product is needed to form normal type-Ⅱ collagen.The gene responsible for SEDT is SEDL,mapped to the short arm of the X chromosome(Xp22).This paper briefly reviews the progress in the studies of molecular genetics of SEDC,SEDT and other rare forms of SED,which might provide some practical help for genetic and prenatal diagnoses of SED.

Objective To study the correlation of mitochondrial DNA mutation of spermatozoa and change of mitochondria-ultrastructure with male infertility. Methods The techniques of PCR and DNA sequence analysis were used to detect MTCYB and MTATP-6 fragments of 76 samples of semen with poor motility from infertile male.Of these samples five were identified with mitochondrial DNA deletion and transmission electron microscopic observations were made. Results Under the electron microscopic observations the 5 samples were all seen with abnormal volume of mitochondria in most spermatozoa tails either small or big, disorderly located and asymmetrically distributed;the axonemal structures of sperm wrapped in layers of mitochondria. These samples of sperm were noticeably different in form from those from fertile male. Conclusion Sperm mitochondria-ultrastructure change were observed in samples of sperm mitochondrial DNA mutation.Sperm mitochondrial mutation and its mitochondria-ultrastructure affect the energy supply of sperms during the process of fertilization which may result in male infertility.;

The development and wide application of assisted reproductive techniques(ART) help many couples suffered from infertility and/or sterility to get baby.Meanwhile,the usage of ART led to much ethic problem.We,hence,investigate the strategies to deal with the ethic problem in ART correctly.

A) in COL1A1 gene resulting in OI in a Chinese family. The detailed molecular and clinical features will be useful for extending the evidence for genetic and phenotypic heterogeneity in OI and exploring the phenotype-genotype correlations in OI.

Gondadal differentiation is genetically determined in humans. Sex is determined when the bipotential embryologic tissues differentiate into testes or ovary. SRY, a gene located on the Y chromosome, triggers a complex genetic cascade leading to testicular differentiation. However, only a minority of 46, XY sex reversal patients can be explained by SRY mutations, suggesting that other genes influencing sex determination are to be discovered. Recent studies show that testis differentiation requires insulin receptor family function in mice. SRY normally requires two distinct NLS-dependent nuclear import pathways to reach sufficient levels in the nucleus for gonadal differentiation.
Active Transport, Cell Nucleus ; Female ; Gene Expression Regulation ; Genes, sry ; physiology ; High Mobility Group Proteins ; genetics ; physiology ; Humans ; Male ; SOX9 Transcription Factor ; Sex Differentiation ; Transcription Factors ; genetics ; physiology

Objective:To investigate a large Chinese family in which 9 patients over 4 generations were diagnosed with a form of autosomal dominant spondyloepimphyseal dysplasia(SEMD).Mothods:X-Ray radiograph of proand at 18-month showed absence of secondary ossification centra of femoral heads.His father at 24-year presented severe spondyloepiphyseal changes that principally involved the vertebral bodies,the femoral necks and femoral heads and characterized by generalized platyspondyly with thoracolumbar scoliosis,irregular femoral necks,absent ossification of femoral heads,flat acetabular roofs and coxa vara.The other patients had similar clinical and radiological features.Haplotyping was performed with leukocyte DNA for 5 micosatellite repeat markers from chromosome 12 and the result showed COL2A1 gene as a candidate gene.A total of 54 exons and promoter of COL2A1 gene were amplified and sequenced from all patients and available normal relatives.In addition,exon 23 of COL2A1 gene was amplified and sequenced from 10 controls simultaneously.Results:All patients were identified a 1510(G→A) transition in exon 23 of COL2A1 gene that caused a change from a COL2A1 coding region in available glycine to serine at amino acid position 504.No mutation was found in the normal relatives and 10 controls. Conclusion:The mutation of COL2A1 gene is responsible for this form of SEDC of the family.This is the first familial report of SEDC relating to 1510G→A mutation of COL2A1 gene.The detailed clinical radiogram data will be useful for extending the phenotypic spectrum of type Ⅱcollagenopathies.

Objective: To report a case of azoospermia with a karyotype of 45,X,der(Y)t(Y;13)(q11.2;q12),-13,accompanied with slight bilateral gynecomastia and multiple nodules.Methods: The karyotype was identified by karyotyping and FISH,and the breakpoints of the Y chromosome and the copy number of the BRCA2 gene in 13q12 determined by PCR-STS and DNA polymorphic analysis.The testis and nodule tissues of the patient were obtained for biopsy.Results: FISH confirmed SRY and centromere of the Y chromosome on the questionable 13 chromosome and the karyotype to be 45,X,der(Y)t(Y;13)(q11.1;q12),-13.ish der(Y)(SRY+,DYZ3+,wcp13+).PCR-STS showed the deletion of regions AZFa,b and C,with a breakpoint located inYq11.1 below sY82.No deletion of the BRCA2 gene was observed.The patient was diagnosed with Sertoli cell-only syndrome by testicular biopsy and with angiolipomata by pathological examination of the nodule tissue.Conclusion: The patient's phenotype of complete masculinization could be attributed to presence of the SRY gene,and his azoospermia with small testis to the absence of a fragment from Yq11.1 to Yqter.However,the molecular mechanism of angiolipoma remains unknown.

Objective To report a familial dentinogenesis imperfecta type Ⅱ (DGI type Ⅱ) with a novel splicing mutation in DSPP (dentin sialophosphoprotein) gene.Methods Based on the result of linkage analysis performed previously to map the candidate gene DSPP in the family, the promoter,the first four exons and exon-intron boundaries of DSPP were directly sequenced for the members of the DGI type Ⅱ family. Denaturing high performance liquid chromatography (DHPLC) analysis was performed to confirm the results of sequencing.Results A novel splicing mutation of 23 bp deletion in intron 2 of DSPP gene was identified by DNA sequence analysis. The mutation changed acceptor site sequence from CAG to AAG, and might result in functional abolition of possible branch point site in intron 2. DHPLC result was consistent with that of sequencing. The mutation may be identified in all affected individuals, but not found in normal members of the family and 50 controls.Conclusion These results suggest the deleted mutation of DSPP gene causes DGI type Ⅱ in the family. The mutation has not been reported before.

Objective To report the prenatal molecular diagnosis for two gravida in a family with spondylepiphyseal dysplasia congenita(SEDC)caused by G504S mutation of COL2A1 gene.Methods DNA of the two fetuses was extracted from amniotic fluid at the 19+3 and 18+6 weeks of gestation respectively.Direct sequencing of two samples were performed after amplifying exon 23 of COL2A1 containing the potential mutation.The femur length and biparietal diameter of the first fetus were measured by sonographic scans every two weeks from 17+3 weeks to 27+3 weeks of gestation,and for the second fetus these parameters were measured from 16+1 to 19+1 weeks of gestation.Results Sequncing analysis revealed the first fetus and his mother presented the same mutation which is specifically associated with SEDC,but the second fetus did not show the mutation of COL2A1 gene.Biparietal diameters of the both fetuses were appropriate for gestational age.Femur length of the second fetus was normal for gestational age but that of the first fetus was shortened evidently after the 23 week of gestation.The parents of the first fetus determined to terminate the pregnancy.A medical termination was carried out at 27+5 weeks of gestation and a male fetus with a relatively large head and short limbs was delivered.The radiological findings of the fetus were consistent with SEDC including generalized platy spondesand shortened long bones.Conclusions Prenatal molecular diagnosis is important for the fetus with risk of SEDC and useful for genetic counseling.Genotype of fetus with risk of SEDC can be identified before sonographic scan.Molecular genetic analysis in conjunction with sonographic monitoring was helpful in prenatal diagnosis of SEDC.

Objective:To investigate the expression of annexin 5 in rat testis after removing submandibular gland in rats. Methods:On day 14,28 and 42 after the operation,the changes of annexin 5 expression in rat testis were analyzed by Western blot and Immunohistochemistry.Results:Western blot showed that there was a 27.5% and a 35.2% significant increase(P