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An analytical relationship between the contrast in polychromatic image speckle patterns and the positions of the diffuse object's surface normal, the illumination, and the axis of the imaging system has been obtained. When the axis coincides with the direction in which the mirror reflects the illumination about the normal, the contrast in the image speckle pattern is the greatest. Some qualitative experimental results are also given.

It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent. The current study aimed to evaluate the relationship between GWG and risk of ASD in offspring. Four electronic databases were searched up to August 28 2018 to identify observational studies reporting the association between GWG and risk of ASD in the offspring. Nine studies which met the inclusion criteria were included in the systematic review. Finally, five studies with a total of 3793 children with ASD were included in the meta-analysis. The-results indicated that excessive GWG might increase the risk of ASD in offspring (p = .0008, OR  =  1.23, 95% confidence interval (CI) 1.09-1.38). More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG.Impact statementWhat is already known on this subject? It has been revealed that gestational weight gain (GWG) influences the risk of autism spectrum disorder (ASD) in the offspring, but the findings are inconsistent.What the results of this study add? This is the first systematic review and meta-analysis on the association between GWG and ASDs in offspring. This study suggested that excessive GWG was associated with higher risk of ASD in offspring.What the implications are of these findings for clinical practice and/or further research? More high quality cohort studies are needed to confirm this result. This research has the potential to inspire new research on ASD and promote efforts to design appropriate interventions against excessive GWG. [ABSTRACT FROM AUTHOR]

Aim: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant., Methods: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant., Results: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied., Conclusion: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease., Competing Interests: Conflicts of Interest: Li J, None; Hu YQ, None; Cheng HB, None; Wang T, None; Kuang LH, None; Huang T, None; Yan XH, None., (International Journal of Ophthalmology Press.)

Objective: To study the hematologic and molecular features of 14 patients with hemoglobin (Hb) variants, so as to provide reference data for its laboratory screening., Methods: A total of 1 029 samples were screened by high performance liquid chromatography (HPLC) on the Bio-Rad VariantⅡHPLC system. GAP-PCR and reverse dot blot (RDB) were used to detect common mutation of α and β globin gene in Chinese. DNA sequencing for α and β globin gene was simultaneously performed in samples with abnormal spectrum peak and negative thalassemia gene., Results: In 1 029 samples, 10 types of structural Hb variants were detected in14 cases (1.36%), including 1 case of Hb E / β- thalassemia, 1 case of Hb E /α- thalassemia (HbH disease), 2 cases of HbG-Taipei, 2 cases of Hb Q-Thailand, 2 cases of Hb Youngstown, 1 case of Hb Guangzhou-Hangzhou, 1 case of Hb M-Boston, 1 case of Hb G-Siriraj, 1 case of Hb J-Baltimore, 1 case of Hb J-Sicilia and 1 case of Hb Tamano., Conclusion: The occurrence of abnormal structural Hb variants with many genotypes in Shanghai is unique. Except for Hb E, Hb Youngstown, and Hb M-Boston, other types of heterozygous are normal in phenotypes, and symptoms such as hemolysis and anemia often occur when other diseases are combined.

Behçet's disease is a chronic, relapsing, systemic vasculitis of unknown aetiology. Patients present manifestations of gastrointestinal complications, including mouth lesions, small and large intestinal lesions, and vascular lesions in the abdomen. In some cases, the intestinal ulcers of patients with Behçet's disease are indistinguishable from those of Crohn's disease, tuberculosis, vasculitis and other diseases. In this article, we present a case of atypical Behçet's disease with a complicated medical history and multisystem damage, for the purpose of better management of this disease.

Objective: To evaluate the short-term safety of intravitreous bevacizumab (Avastin) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (ARMD)., Methods: Single-center, uncontrolled clinical study. Five ARMD patients (5 eyes) with subfoveal CNV and best-corrected VA (BCVA) less than 0.1 were participated. Patients were treated with an intravitreous injection of bevacizumab (1.5 mg, 0.06 ml). Ophthalmologic evaluations included BCVA test, ocular examination, intraocular pressure (IOP) measurement, optical coherence tomography (OCT) imaging and fluorescein angiography (FFA)., Results: There were no ocular or systemic adverse events observed, except a mild elevation of IOP [26 mm Hg (1 mm Hg = 0.133 kPa)] in 1 case on the 3rd day after injection, which was controlled by topical medication. One out of 5 eyes had a significant improvement of BCVA (from 0.1 improved to 0.4) in one week after injection. By 2 months, the BCVA increased in 4 cases (increased 1 to 6 lines) and 3 of them remained stable for 4 to 6 months and 1 decreased at the 4 th month post injection. The thickness of central retina reduced 5.9% to 41.4% and FFA revealed a remarkable reduction or an absence of leakage from CNV in 3 eyes by the 4th month., Conclusion: Our preliminary results are promising, showing that intravitreous bevacizumab therapy is well tolerated with an improvement in VA, OCT, and FFA outcomes. A multi-center randomized controlled clinical trial is needed to evaluate the long-term safety and effectiveness of intravitreous bevacizumab therapy on neovascular ARMD.

Objective: To investigate the mechanism of clinical haemorrhage in an inherited coagulation factor VII (FVII) deficiency and tissue factor abnormality pedigree., Methods: All exons, exon-intron boundaries and the 3', 5' untranslated sequences of FVII and tissue factor (TF) genes were amplified by PCR and sequenced directly. Any mutation identified by direct sequencing was confirmed by reverse sequencing. FVII cDNA of the proband was synthesized with random primers and amplified by nest PCR., Results: 55C-->T heterozygous mutation located in promoter of FVII gene was identified in the proband. The heterozygous mutation was derived from his mother. Tracing the other pedigree members found that his sister had the same heterozygous mutation and the others had wild-type FVII genes. A 9363 C-->T (Arg131Trp) heterozygous polymorphism in TF gene, which was 2.63% frequency of T allele polymorphism, was found in all of the pedigree members., Conclusion: It was the first report that the -55C-->T heterozygous mutation in FVII gene and the Arg131Trp heterozygous polymorphism in TF gene explained the clinical symptom of the proband.

Background and Objectives: Most secreted proteins, including coagulation factor X (FX), are synthesized with a signal peptide, which is necessary for targeting the nascent polypeptide into the endoplasmic reticulum. Characterization of naturally occurring mutations may provide insights into the functional roles of the amino acids in the signal peptide., Design and Methods: A 52-year old male patient with type I FX deficiency was studied. Mutations were searched for by FX gene (F10) sequencing. The wild-type and the mutant FX proteins were expressed in transfected cells and then immunological assays were performed. Pulse-chase experiments and cell-free expression studies were conducted to determine the cellular fate of the mutant FX molecules., Results: The patient we studied was homozygous for a substitution of arginine for serine at codon -30 in the signal sequence of F10. Immunoassays detected low FX antigen levels in both the conditioned media and lysates of the cells expressing the mutant protein. Pulse-chase analysis showed that only trace amounts of the mutant FX protein were detectable in the conditioned media, and that the mutant molecules did not accumulate inside the cells either. The results of cell-free expression studies showed that although the transcription and translation of the mutant construct were normal, no post-translational processing, such as N-linked glycosylation, occurred in the presence of microsomes., Interpretation and Conclusions: These findings suggest that substitution of a neutral polar amino acid, serine by arginine, in the hydrophobic core of FX signal peptide severely impairs the ability of the protein to enter the endoplasmic reticulum and results in FX deficiency.

Objective: To identify the phenotype and the gene mutation in a kindred with antithrombin (AT) deficiency., Methods: Immuno-nephelometry and chromogenic assay were used to detect the plasma level of AT antigen (AT: Ag) and activity (AT: A), respectively. All the seven exons and intron-exon boundaries of AT gene from the propositus were amplified by PCR and direct sequencing of the PCR pro-ducts was performed. Corresponding PCR fragments from the kindred were also sequenced directly. Megaprimer method was used to construct the mutant AT cDNA expressing vector from normal plasmid pCRII AT cDNA. The normal and mutant AT plasmid were transiently transfected into Cos-7 cells and AT: Ag was detected in supernatant and lysate of transfected cell with ELISA., Results: The plasma level of AT: Ag and AT: A for the propositus were 179 mg/L and 42.3%, respectively. A heterozygous G13328A missense mutation in exon 6 was identified, which led to the substitution of Thr (ACC) 404 for Ala (GCC). The sequencing results from the pedigree suggested that three other members also had the mutation. The level of AT:Ag in supernatant and lysate from cells transfected with mutant AT cDNA was 40% and 68% of that of normal AT cDNA transfected cells., Conclusion: This is an unreported AT gene mutation in China, which causes type I hereditary antithrombin deficiency and thrombosis in the proposita.

Objective: To study the molecular mechanism of antithrombin (AT) gene C2759T (Leu99Phe) mutation causing AT deficiency., Methods: A mutated AT cDNA expression plasmid ATM2759 was constructed by mega-primer method. ATM2759 and wild type AT cDNA expression plasmid ATN were transfected into COS7 cells or CHO cells by using Superfect reagent respectively for in vitro expression study and immunofluorescence assay., Results: The antigen levels of AT (AT:Ag) in the cell lysate of ATM2759 transfected COS7 cells and the cell culture supernatant were 174.97% and 35.63% of that of ATN transfected COS7 cells respectively, whereas the AT activity in the cell culture supernatant was 47.73% of the control's. Immunofluorescence analysis showed that the fluorescence intensity was significantly higher in ATM2759 transfected CHO cells than in those transfected with ATN., Conclusions: Leu99Phe substitution may not affect the binding capacity of AT with heparin. Secretion defect and intracellular accumulation of the mutated AT protein might be the mechanisms of this mutation causing AT deficiency.

Objective: To identify gene defect in a Chinese pedigree of hereditary coagulation factor XI (FXI) deficiency., Methods: The peripheral blood samples were collected from the proband and her family members. The plasma PT, APTT, FXI:C and FXI:Ag were assayed. The FXI gene exons and exon-intron boundaries of the proband were amplified by PCR and then sequenced directly. The mRNA of FXI in the peripheral blood was analyzed with RT-PCR., Results: The proband and some of her family members had prolonged APTT. The plasma FXI:C and FXI:Ag of the proband, her brother and her parents were lower than 10% and 50% of the normal values, respectively. Nucleotide sequence analysis revealed that the proband and her brother had a homozygous mutation of IVS J-4delgttg in FXI gene. The mutation was inherited from her parents who were heterozygotes. The mutation was not found in 60 normal subjects. No FXI mRNA was detected in peripheral blood sample of the proband., Conclusion: The IVS J-4delgttg is a novel mutation causing FXI deficiency, which may interfere with mRNA splicing.

Objective: To identify gene mutations of a pedigree with inherited factor V (FV) deficiency., Methods: The activated partial thromboplastin time (APTT), prothrombin time (PT), FV activity (FV:C) and FV antigen (FV:Ag) tests were performed for phenotypic diagnosis. The genomic DNA was extracted from the peripheral blood of the proband and all the 25 exons and their flanks of FV gene were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations were further confirmed by restriction enzyme digestion., Results: APTT, PT, TT, FV:C, FV:Ag of the proband were 249.2 s, 46.6 s, 17.9 s, 0.1% and 1.5%, respectively. FII, FVII, FVIII, FIX, FX activities, vWF and Fg were within normal ranges. Taking the GenBank Z99572 sequence as the reference, four mutations were identified in FV gene of the proband. They were a heterozygous two bases deletion in exon 13 (2238 approximately 2239delAG) introducing a frameshift and a premature stop at codon 689, and a heterozygous missense mutation in exon 23 (G6410T) resulting in the substitution of Gly for Val at codon 2079, respectively. The proband's father and mother were heterozygous for G6410T and for 2238 approximately 2239delAG, respectively., Conclusion: The severe FV deficiency of the proband is caused by a frameshift mutation of 2238 approximately 2239delAG and a missense mutation of G6410T, which haven't been identified before.

Objective: To analysis the clinical features of gastrointestinal (GI) carcinoid tumor in different pathological types, and to improve the level of its diagnosis and treatment., Methods: Retrospectively analysis 36 cases of GI carcinoid in Peking Union Medical College Hospital from 1982 to 2003, according to the International Classification of Disease for Oncology (ICD-O). The 36 cases were divided into carcinoid group and malignant carcinoid group. Their clinical presentation, metastasis, age, its ratio in gastrointestinal endocrine and non-endocrine tumor were compared., Results: (1) Ratio: the ratio of GI carcinoid in digestive system non-endocrine tumor was 0.35%, in endocrine tumor was 10.20%. (2) Age: the mean age of the malignant carcinoid group was (55.8 +/- 12.8) years old and carcinoid group was (45.1 +/- 12.0). The age of the malignant carcinoid group is significantly higher than that of the carcinoid group. (3) Sites: the rectum carcinoid (63%) was the most common site of the overall GI carcinoid, the gastric (35%) and colonic (25%) carcinoid in the malignant carcinoid group were found more than that in carcinoid group. (4) Metastasis: the lymphonode and liver (60%) were most common sites of malignant carcinoid tumor. The ratio of metastasis from stomach and colon was higher than that from the other gastrointestinal sites. (5) DIAGNOSTIC METHODS: most of the GI carcinoid tumors were diagnosed by the colonoscopy. The rectal touch should not be neglected. (6) Carcinoid syndrome: The incidence of carcinoid syndrome was quite low and often occurred in malignant carcinoid tumor., Conclusions: The overall incidence of GI carcinoid tumor makes up 0.35% of gastrointestinal tumor. It is not common disease but not rare. The rectum is most common site of carcinoid tumor. Most of the gastric and colonic carcinoid tumor was belonging to malignant. The mean age of malignant carcinoid tumor was older with the metastasis of lymphonode and liver. The carcinoid syndrome often occurred in malignant carcinoid tumor.

Objective: To explore the molecular mechanisms involved in a pedigree with inherited coagulation factor X (FX) deficiency., Methods: The activated partial thromboplastin time (APTT), prothrombin time (PT), FX activity (FX:C) and FX antigen (FX:Ag) test were adopted for phenotype diagnosis. All the 8 exons, intron/exon boundaries and the 5'untranslated regions (UTR) of the FX gene were amplified by polymerase chain reaction (PCR) from the genomic DNA extracted from the peripheral blood of the propositus. The PCR products were screened by direct sequencing. The mutation was confirmed by allele specific PCR (ASPCR)., Results: The phenotype of the propositus was identified as FX deficiency (type II). Two novel FX gene mutations were detected in the propositus: one was a donor site splice mutation in intron 1 (IVS1 + 1G-->A), another was a missense mutation 1185G-->A in exon 8 (Arg347His)., Conclusion: The FX deficiency of the propositus is caused by double heterozygous mutations IVS1 + 1G-->A and Arg347His.

Background: We identified the gene mutations in two Chinese pedigree of type I hereditary protein C deficiency and type I hereditary antithrombin deficiency., Methods: The plasma level of protein C activity (PC:A), protein C antigen (PC:Ag), protein S activity, antithrombin activity (AT:A) and antithrombin antigen (AT:Ag) of propositi and two family members were detected using ELISA and chromogenic assay, respectively. All exons and intron-exon boundaries of protein C gene and antithrombin gene were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus., Results: The plasma PC:A and PC:Ag of propositus 1 was 26% and 1.43 mg/dl, respectively. The PC:Ag and PC:A of his father were normal. The decreased PC:A level was seen in his mother and 4 of his maternal pedigree. PS:A and AT:A were all normal in pedigree 1 members. A C5498T heterozygous mutation in exon 3 of protein C gene, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in propositus 1 and 8 of his relatives. The plasma AT:A and AT:Ag of propositus 2 was 48.6% and 10.4 mg/dl, respectively. The reduced AT:A and AT:Ag levels were found in his father and 5 of paternal pedigree. PC:A, PC:Ag and PS:A were all in normal range. A heterozygous 13387-9G deletion in exon 6 of antithrombin gene was identified in propositus 2. This mutation introduced a frameshift and a premature stop at codon 426 and existed in 6 members of pedigree 2., Conclusion: The C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary protein C deficiency. The 13387-9G deletion, a novel mutation, can cause antithrombin deficiency and thrombosis.

Objective: To determine the lead concentration in the air (pbA) at the workplace and the renal function of lead exposure workers., Methods: The lead concentration in the air of 11 printing plants, 4 smelteries and 2 lead mines were measured. Screening urinalysis was performed in 1190 long term lead exposed workers with urine sugar, protein and sigements. It one of the three was abnormal, the workers were given examination of renal function. The relationship between pbA and renal function were confirmed by mutiple linear., Results: The concentrations of pbA in the printing plants, smelteries and lead mines were 0.07 mg/m3, 0.26 mg/m3 and 0.66 mg/m3 respectively. Altogether 157 cases had one and more abnormal renal function. The correlation of concentration PbA in the workplace and the renal function of lead exposure workers was shown (R = 0.894, P < 0.001, R2 = 0.799). The correlation coefficient of skewness of showed that PbA and Bpb. Upb. Bun Scr Usug. Ubeta2MG were positively correlated (P < 0.01 approximately 0.001); Ccr was negatively correlated (P =0.05). Upro, UNAG and Ualb were nonsignificant., Conclusion: The lead concentration in the air at the workplace is related to the renal functions of lead exposure workers. It is important to decrease the lead environment and to prevent renal damage.

Objectives: To identify the FXI gene mutations in two Chinese pedigrees of congenital factor XI deficiency., Methods: The peripheral blood samples were collected from the probands and their family members and the plasma FXI:C and FXI:Ag were determined. All the exons and exon-intron boundries of FXI gene were amplified with PCR and sequenced thereafter., Results: A nonsense mutation Trp228stop and two missense mutations Glu323Lys and Leu172Pro were disclosed in the two pedigrees. All mutations existed in a heterozygous state., Conclusion: The FXI gene mutations Trp228stop, Glu323Lys and Leu172Pro attribute to the pathogenesis of the congenital factor XI deficiency in Chinese. The Leu172Pro is identified for the first time.

Objective: To investigate the pathogenesis of inherited coagulation factor VII (FVII) deficiency., Methods: The diagnosis was validated by coagulant parameter assay. FVII gene mutations were analysed in the proband by DNA direct sequencing of PCR products of all exons, exon-intron boundaries and the 3', 5'untranslated sequences. The mutations were confirmed by reverse sequencing. The ectopic transcripts of RT-PCR were used to confirm the characteristics of the mutation in non-canonical splice site (IVS1a + 5g > a)., Results: Double heterozygous mutations in the propositus were identified: a T to G mutation at position 10961, resulting in His348Gln substitution, a non-canonical splice site (IVS1a + 5g > a) mutation, causing the new model of splice and frameshift mutation., Conclusion: Double heterozygous mutations of His348Gln and IVS1a + 5g > a were identified in a propositus, the splicing pattern of the IVS1a + 5g > a mutation was reported for the first time.

Objective: To investigate the mechanisms of two novel missense mutations of factor XIIIA subunit gene (Arg77-->Cys,Ser413-->Trp) in the pathogenesis of hereditary factor XIII deficiency., Methods: Site-directed mutagenesis was conducted to obtain 2 mutant human XIII A recombinant plasmids, mut-PCI/FXIIIA. Normal wild type factor XIII A recombinant plasmid, wt-PCI/FXIIIA, and mut-PCI/FXIIIA, were transfected into cultured COS7 cells line, renal fibroid cell of African green monkey using Superfect reagent respectively, The expression levels of DNA, RNA and protein of human factor XIII, both wild type and mutant, were detected by PCR, RT-PCR and Western blotting. Pulse-chase experiment was used to look into the changing of factor XIII A in the cytoplasm. Factor XIIIA activity was assayed by Biotin-pentylamine incorporation technique., Results: The mRNA levels of the two mutants in transfected cells were similar to that of the wild type factor XIIIA. But the amount of mutant factor XIIIA protein and its activity in cells decreased markedly, even disappeared. Pulse-chase experiment revealed that at the two mutants existed chase time 0.5 h and 1 h considerable amounts in cells and then disappeared rapidly later., Conclusion: The 2 mutations of the factor XIIIA cause the instability, degradation, and rapid disappearance of FXIIIA in cytoplasm, thus resulting in hereditary factor XIII deficiency.

Objective: To identify the mutations of fibrinogen genes in a Chinese family with inherited afibrinogenemia., Methods: Samples of peripheral blood were collected from 17 members of 3 generations in a Chinese family with inherited afibrinogenemia, including the proband, female, aged 8. All the exons and exon-intron boundaries of the three fibrinogen genes were analyzed by direct sequencing., Results: The sequencing results of the proband revealed compound 2 heterozygous mutations in fibrinogen FGA gene, one being a splice mutation (g.1892-1899delAGTAorGTAA) in the boundary between exon3 and intron3 of the FGA gene and traced back to her patriline and the other being a 1,238 bp large deletion (g.1978-3215) in the same gene and originating from her matriline., Conclusion: Inherited afibrinogenemia is caused by the compound heterozygous deletion in the fibrinogen FGA gene.

Objective: To identify the gene mutation in a Chinese pedigree of type I hereditary protein C deficiency., Methods: The plasma levels of protein C activity (PC:A), protein C antigen (PC:Ag), protein S activity, and anti-thrombin activity (AT:A) of the propositus, male, aged 7, and 11 members of the pedigree were detected using ELISA and chromogenic assay respectively. All of the nine exons and intron-exon boundaries of protein C gene of the propositus were analyzed by direct sequencing of the corresponding amplified PCR products in DNA from the propositus. Restriction enzyme site analysis was used to confirm the mutation., Results: The plasma concentrations of protein C activity and antigen of the propositus were 26% and 1.43 g/L respectively. The PC:Ag and PC:A of his father were normal. Decreased PC:A level was seen in his mother and 4 of his maternal pedigree. PS:A and AT:A were all normal in all of the pedigree members. A C5498T heterozygous mutation in exon 3, resulting in the substitution of Arg for Trp at the 15th amino acid, was identified in the propositus and 8 of his relatives. This mutation was confirmed by restriction enzyme site analysis. Mutations C/T at position 2405, A/G at position 2418, and A/T at position 2583 in the protein C promoter region were confirmed in the propositus and all members of the pedigree., Conclusion: C5498T heterozygous mutation in exon 3 of protein C gene, first reported in China, leads to type I hereditary.

Objective: To identify the genetic mutations of a severe inherited coagulation factor VII (FVII) deficiency pedigree., Methods: The diagnosis was validated by coagulant and haemostatic parameters. FVII gene mutations were screened in the propositus and his family members by DNA direct sequencing and confirmed by digestions of the restriction enzymes of the PCR production., Results: Two heterozygous missense mutations were found in the propositus of the pedigree: a G to T transversion at position 9482 in exon 6 and a C to T mutation at position 11348 in exon 8 resulting in the amino acid substitution of Arg152 with Leu and Arg304 with Trp, respectively. A heterozygous single nucleotide deletion (C) at position 11487-11489(CCC) within exon 8 was identified, which predicted the frameshift mutation at position His351 followed by the changes of six corresponding amino acids and appearance of a premature protein caused by stop codon. The heterozygous mutations identified in the proband were derived from his father (Arg152 to Leu) and his mother (Arg304 to Trp mutation) and a heterozygous deletion (C) at position 11487-9(CCC). By tracing the other pedigree members, it was found that his grandmother had a heterozygous mutation of Arg304Trp and a heterozygous polymorphism of Arg353Gln and his grandfather had a heterozygous Arg152Leu mutation., Conclusion: Three heterozygous mutations were found in a pedigree with hereditary coagulation factor VII deficiency. Arg152Leu and deletion C at position 11487-9(CCC) were novel mutations.

Objective: To investigate the gene mutations in a pedigree with inherited prothrombin (FII) deficiency., Methods: The activated partial thromboplastin time (APTT), prothrombin time (PT), FII activity (FII:C) and FII antigen (FII:Ag) test were used for phenotype diagnosis. The genomic DNA was extracted from the peripheral blood of the propositus. All the 14 exons, intron/exon boundaries and the 5' and 3' untranslated regions (UTR) of the prothrombin gene were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations detected were further confirmed by restricted enzyme digestion. One hundred and three healthy blood donors were used as controls., Results: The phenotype of the propositus was prothrombin deficiency (type I). With reference to the prothrombin nucleotide sequence published by Degen & Dacie, three variations were found in the FII gene of the propositus. Among them, the novel mutation was a homozygous A601G subtitution in exon 2., Conclusion: The prothrombin deficiency of the propositus is caused by a homozygous Glu29 to Gly mutation in the prothrombin gene.

Objective: To investigate the genotypes of mutations of an inherited coagulation factor VII(F VII) deficiency pedigree., Methods: The diagnosis was validated by coagulant parameters. F VII gene mutations were analysed in the proband and her family members by DNA direct sequencing. The PCR fragments were cleaved by the Msp I restriction enzyme to confirm the mutations detected by sequencing was performed in this study., Results: Double heterozygous mutations at the same coding site of amino acid were detected in propositus of the pedigree: a C to T mutation at position 11348 resulting in Arg304Trp substitution combined with a G to A mutation at position 11349 resulting in Arg304Gln substitution. Her farther had a G to A mutation at position 11349 and her mother had a C to T mutation at position 11348, respectively. Both were heterozygous mutations. One of her brothers had normal genotype, the other brother and all her three offsprings had heterozygous mutations., Conclusion: Double heterozygous mutations coding the same amino acid were found in a pedigree with hereditary coagulation factor VII deficiency.

Objective: To identify the factor XI gene mutation in a Chinese pedigree of congenital factor XI deficiency., Methods: The peripheral blood samples were collected from the proband and her family members and the plasma FXI:C and FXI:Ag were assayed. All the exons and their adjacent intron sequences of factor XI were amplified with PCR and sequenced thereafter., Results: Two novel nonsense mutations TGG-->TGA (Trp228stop) and TGG-->TAG (Trp383stop) were identified in the family., Conclusion: The compound heterozygous Trp228stop and Trp383stop may attribute to the pathogenesis of the congenital factor deficiency.

Objective: To discover the gene mutations of a pedigree with inherited factor V (FV) deficiency., Methods: The activated partial thromboplastin time (APTT), prothrombin time (PT), FV activity (FV:C) and FV antigen test were adopted for phenotype diagnosis. The genomic DNA was extracted from the peripheral blood of the 16-year-old propositus, female. All the 25 exons and their flanks in the FV gene of the propositus were amplified by polymerase chain reaction (PCR). The PCR products were screened by direct sequencing and the mutations were further confirmed by restricted enzyme digestion. Six persons in the pedigree (grandfather, grandmother, father, mother, uncle, and aunt) were examined too. 108 healthy blood donors were used as controls., Results: The APTT, PT, FV:C, and FV:Ag of the propositus were 126.6s, 42.8s, 0.3% and 1.3% respectively. The Fbg and FII, FVII, FVIII, FIX, FX activities were in normal range. FV:C of the members of the pedigree was 36% - 70%, and the FV:Ag of the pedigree members was 26.4% - 45.3% that of the mixture of 30 normal plasma samples. Taking the GeneBank Z99572 sequence as the reference, totally five variations in the FV gene were found in the propositus. The mutations, A1348G and 4887 approximately 8delG, were traced to her father and her mother respectively. No 1348G-->T mutation was found in the 108 controls., Conclusion: The FV deficiency of the propositus is caused by missense mutation of G1348T and frameshift mutation of 4887 approximately 8delG, which haven't been identified previously.