Novel splice site and nonsense variants in PKHD1 cause autosomal recessive polycystic kidney disease in a Chinese Zhuang ethnic family.

BACKGROUND: This study aims to report the clinical characteristics of a child with autosomal recessive polycystic kidney disease (ARPKD) within a Chinese Zhuang ethnic family. METHODS: We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Candidate pathogenic variants were validated by Sanger sequencing. RESULTS: We identified previously unreported mutations in the PKHD1 gene of the proband with ARPKD through WES: a splice site mutation c.6809-2A > T, a nonsense mutation c.4192C > T(p.Gln1398Ter), and a missense mutation c.2181T > G(p.Asn727Lys). Her mother is a heterozygous carrier of c.2181T > G(p.Asn727Lys) mutation. Her father is a carrier of c.6809-2A > T mutation and c.4192C > T(p.Gln1398Ter) mutation. CONCLUSIONS: The identification of novel mutations in the PKHD1 gene through WES not only expands the spectrum of known variants but also potentially enhances genetic counseling and prenatal diagnostic approaches for families affected by ARPKD.

A novel discriminant algorithm for differential diagnosis of mild to moderate thalassemia and iron deficiency anemia.

BACKGROUND: Mild to moderate thalassemia trait (TT) and iron deficiency anemia (IDA) are the most common conditions of microcytic hypochromic anemia (MHA) and they exhibit highly similar clinical and laboratory features. It is sometimes difficult to make a differential diagnosis between TT and IDA in clinical practice. Therefore, a simple, effective, and reliable index is needed to discriminate between TT and IDA. METHODS: Data of 598 patients (320 for TT and 278 for IDA) were enrolled and randomly assigned to training set (278 of 598, 70%) and validation set (320 of 598, 30%). Stepwise discriminant analysis was used to define the best diagnostic formula for the discrimination between TT and IDA in training set. The accuracy and diagnostic performance of formula was tested and verified by receiver operating characteristic (ROC) analysis in validation set and its diagnostic performance was compared with other published indices. RESULTS: A novel formula, Thalassemia and IDA Discrimination Index (TIDI) = -13.932 + 0.434 × RBC + 0.033 × Hb + 0.025 ×MCHC + 53.593 × RET%, was developed to discriminate TT from IDA. TIDI showed a high discrimination performance in ROC analysis, with the Area Under the Curve (AUC) = 0.936, Youden' s index = 78.7%, sensitivity = 89.5%, specificity = 89.2%, respectively. Furthermore, the formula index also obtained a good classification performance in distinguishing 5 common genotypes of TT from IDA (AUC from 0.854-0.987). CONCLUSION: The new, simple algorithm can be used as an effective and robust tool for the differential diagnosis of mild to moderate TT and IDA in Guangxi region, China.

A clinical update of compound heterozygosity for hemoglobin Hekinan II [a27(B8)Glu-Asp; HBA1: c.84G>T] variant in China.

BACKGROUND: Hemoglobin (Hb) Hekinan II (A27; Glu-Asp) is an α-chain variant, and its interaction with the common Southeast Asian (--SEA/) α-thalassemia (α-thal) deletion is rarely reported. This study provides a clinical update of Hb Hekinan II associated with (--SEA/) α-thal. METHODS: A total of 11 simple heterozygotes and 20 composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal were included based on molecular diagnosis. RESULTS: Hb Hekinan II exhibited a significant increase in hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin content, but a decrease in red blood cell level compared with α+ thalassemia deletion. Compared with (--SEA/) α-thal, composite heterozygotes for Hb Hekinan II and (--SEA/) α-thal showed similar erythrocyte parameters. Both heterozygotes with and without (--SEA/) α-thal showed low Hb A2 level. Hb Hekinan II showed abnormal performance in high-performance liquid chromatography but not in capillary electrophoresis. CONCLUSION: Hb Hekinan II is a benign Hb variant. The heterozygotes exhibit clinically asymptomatic coinheritance with (--SEA/) α-thal having comparable hematological phenotype to simple (--SEA/) α-thal. The combination of hematological and molecular analysis helped to improve the detection rate of this rare variant.

Guideline for diagnosis and management of congenital dysfibrinogenemia.

INTRODUCTION: Congenital dysfibrinogenemia (CD) is characterized by dysfunction induced by an abnormal fibrinogen molecule structure that results in blood coagulation dysfunction. The clinical manifestations of CD patients are asymptomatic, bleeding and thrombosis. The majority of patient are asymptomatic. However, the single fibrinogen detection method is easy to cause missed diagnosis or misdiagnosis of CD patients. The treatment strategies of CD patients with different clinical manifestations are also different. METHODS: Combing the existing experimental diagnosis technology, literature and our research results, a simple and practical CD diagnostic criteria was proposed. And based on the relevant literature and existing treatment guidelines, more comprehensive treatment recommendations are summarized. RESULTS: In this new criteria, combination Clauss method and PT derived method was proposed to detect fibrinogen and its ratio was used to diagnose for CD. Diagnosis also needs to be combined the clinical manifestations, family investigation and genetic testing. According to different clinical manifestation (bleeding, thrombosis or asymptomatic), treatment methods and strategies are different. The treatment of CD patients should consider the patient's personal and family history of bleeding or thrombosis. Treatment of thrombosis and pregnancy may be more challenging. The risk of bleeding and thrombosis should be evaluated and balanced at all times during clinical treatment. These detailed treatment recommendations can provide reference for patients with different clinical manifestations of CD. CONCLUSIONS: The new CD diagnosis criteria and comprehensive treatment recommendations can effectively improve the diagnosis and treatment of CD.

The combined detection of hematological indicators is used for the differential diagnosis of colorectal cancer and benign-colorectal lesions.

OBJECTIVE: This article aims to investigate the clinical value of hemoglobin/red cell distribution width ratio (Hb/RDW), C-reactive protein/albumin ratio (CAR) and plateletcrit (PCT) combined with carcinoembryonic antigen (CEA) in colorectal cancer (CRC) auxiliary diagnosis. METHODS: We retrospectively analyzed in 718 subjects (212 with CRC, 209 with benign colorectal lesions (BCL), 111 with other cancers, and 186 healthy controls). RESULTS: The CAR, PCT, and CEA in the CRC group were higher than those in the BCL, other cancers, and the healthy control group. However, Hb/RDW in the CRC group was lower than the other three groups. Moreover, there were significant differences in Hb/RDW and CEA among different T-N-M stages (all P< 0.05). Multivariate logistic regression showed that low level of Hb/RDW and high level of CAR, CEA, PCT were risk factors for CRC, and are correlated with CRC stage. Additionally, the area under the receiver operating characteristic curve (AUC) of Hb/RDW+CEA (AUC: 0.735), CAR+CEA (AUC: 0.748), PCT+CEA (AUC: 0.807) was larger than that of Hb/RDW (AUC: 0.503), CAR (AUC: 0.614), or PCT (AUC: 0.713) alone (all P< 0.001) in distinguishing CRC from BCL. CONCLUSIONS: Hb/RDW, CAR, PCT, and CEA are independent risk factors for CRC. Hb/RDW, CAR, and PCT combined with CEA have significant value for auxiliary differential diagnosis of CRC and BCL.

Association between total bilirubin/Albumin ratio and all-cause mortality in acute kidney injury patients: A retrospective cohort study.

BACKGROUND: The association between the total bilirubin/albumin (B/A) and the all-cause mortality of critically ill patients with acute kidney injury (AKI) remains unclear. This retrospective study aimed to investigate the relationship between B/A ratio and mortality in patients with AKI. METHODS: The clinical data of AKI patients in the Medical Information Mart for Intensive Care III (MIMIC-III) database were retrospectively analyzed. Patients were divided into the low and high B/A groups (B/A ≤ 0.25 and B/A > 0.25, respectively). The primary outcome was 28-day all-cause mortality, and the secondary outcomes were 60-day, 1-year and 4-year all-cause mortality. Kaplan-Meier survival curves and Cox proportional risk models were constructed to evaluate the effect of B/A on survival outcomes. RESULTS: The 28-day mortality rates were 18.00% and 25.10% in the low and high B/A groups, respectively (P < 0.001). The Kaplan-Meier analysis showed that patients with higher B/A values had higher all-cause mortality risk (log-rank P < 0.0001). The multivariate Cox proportional risk analysis showed that B/A was an independent risk predictor for death at 28 days, 60 days, 1 year, and 4 years. CONCLUSION: B/A is an independent risk factor for increased mortality in patients with AKI and may be used as a predictor of clinical outcomes in AKI.

Third-generation sequencing for genetic disease.

Third-generation sequencing (TGS) has led to a brave new revolution in detecting genetic diseases over the last few years. TGS has been rapidly developed for genetic disease applications owing to its significant advantages such as long read length, rapid detection, and precise detection of complex and rare structural variants. This approach greatly improves the efficiency of disease diagnosis and complements the shortcomings of short-read sequencing. In this paper, we first briefly introduce the working mechanism of one of the most important representatives of TGS, single-molecule real-time (SMRT) sequencing by Pacific Bioscience (PacBio), followed by a review and comparison of the advantages and disadvantages of different sequencing technologies. Finally, we focused on the progress of SMRT sequencing applications in genetic disease detection. Future perspectives on the applications of TGS in other fields were also presented. With the continuous innovation of the SMRT technologies and the expansion of their fields of application, SMRT sequencing has broad clinical application prospects in genetic diseases detection, and is expected to become an important tool for the molecular diagnosis of other diseases.

Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages.

Oncolytic viruses (OVs) for cancer treatment are in a rapid stage of development, and the direct tumor lysis and activation of a comprehensive host immune response are irreplaceable advantages of cancer immunotherapy. However, excessive antiviral immune responses also restrict the spread of OVs in vivo and the infection of tumor cells. Macrophages are functionally diverse innate immune cells that phagocytose tumor cells and present antigens to activate the immune response, while also limiting the delivery of OVs to tumors. Studies have shown that the functional propensity of macrophages between OVs and tumor cells affects the overall therapeutic effect of oncolytic virotherapy. How to effectively avoid the restrictive effect of macrophages on OVs and reshape the function of tumor-associated macrophages in oncolytic virotherapy is an important challenge we are now facing. Here, we review and summarize the complex dual role of macrophages in oncolytic virotherapy, highlighting how the functional characteristics of macrophage plasticity can be utilized to cooperate with OVs to enhance anti-tumor effects, as well as highlighting the importance of designing and optimizing delivery modalities for OVs in the future.

Endoplasmic Reticulum Stress in the Pathogenesis of Hyperglycemia Induced by Thiamine-Responsive Megaloblastic Anemia.

BACKGROUND: Thiamine responsive megaloblastic anemia (TRMA) is a genetic disease caused by SLC19A2 gene mutation. This study aimed to preliminarily explore the relationship between endoplasmic reticulum stress (ERS)-PERK signaling pathway and the pathogenesis of hyperglycemia induced by TRMA. METHODS: Islet ß (INS.1 and ß-TC-6) and HEK293T cell line models with stable overexpression of SLC19A2 and SLC19A2 (c.1409insT) were established. The cells were divided into empty virus group (control), wild-type group (overexpressed SLC19A2), and mutation group (overexpressed SLC19A2 (c.1409insT)). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of ERS-PERK signaling pathway-related proteins, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2 (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islet ß cells. Protein localization was assessed by immunofluorescence staining. RESULTS: Compared with the control group, the mRNA expression levels of SLC19A2 in wild-type and mutant islet ß cells (INS.1 and ß-TC-6) and HEK293T cells were significantly upregulated (all p < 0.05). Compared with the control group and the wild-type group, the mRNA expression levels of GRP78, PERK, eIF2α, ATF4, and CHOP were increased (all p < 0.05) in the mutant islet ß cells; the protein expression levels of PERK, GRP78, and eIF2α were elevated (all p < 0.05). In addition, the results of immunofluorescence staining showed that SLC19A2 (c.1409insT) mutation changed the localization of the proteins in the cells. Thus, they were not located on the cell surface, but in the cytoplasm and nuclei, and protein aggregation occurred in the cytoplasm. CONCLUSIONS: 1. Islet ß and HEK293Tcell lines, stably overexpressing SLC19A2 and SLC19A2 (c.1409insT) mutations, were successfully constructed. 2. SLC19A2 (c.1409insT) mutation could raise the expression levels of ERS-PERK signaling pathway-related proteins (GRP78, PERK, eIF2α, ATF4, and CHOP), and activate apoptosis pathway. 3. SLC19A2 (c.1409insT) mutation could change the localization of proteins and produce protein aggregation in cells. It could lead to protein misfolding and ERS, which would participate in the pathological mechanism of hyperglycemia induced by TRMA.

Long noncoding RNA00324 is involved in the inflammation of rheumatoid arthritis by targeting miR-10a-5p via the NF-κB pathway.

BACKGROUND: Altered expressions of genes in immune cells and synovial tissues are involved in the pathology of rheumatoid arthritis (RA). Long noncoding RNAs act as competing endogenous RNAs and can cause immune disorders. The goal of this study was to reveal the association between noncoding RNA linc00324 and RA, and a plausible action mechanism was proposed. METHODS: RT-qPCR was used to evaluate the expression of linc00324 in peripheral blood mononuclear cells isolated from 50 RA patients and 50 healthy controls, and the correlations between linc00324 level and the clinical indicators were analyzed. Flow cytometry was used to characterize CD4+ T cells. The effects of linc00324 on cytokine production and cell proliferation of CD4+ T cells were evaluated by ELISA assay and Western blot. The interaction between linc00324 and miR-10a-5p was investigated by RNA immunoprecipitation and dual-luciferase assays. RESULTS: The linc00324 expression was significantly enhanced in RA patients, and linc00324 expression was positively correlated with rheumatoid factor and CD4+ T cells. Overexpression of linc00324 promoted CD4+ T cells proliferation, and enhanced chemokine MIP-1α secretion and NF-κB phosphorylation level, whereas knockout of linc00324 blocked CD4+ T cell proliferation and NF-κB phosphorylation. Overexpression of miR-10a-5p led to the decrease of CD4+ T cells proliferation and NF-κB phosphorylation, and reversed the effects of linc00324 on cell proliferation and NF-κB activity. CONCLUSION: Linc00324 was upregulated in RA and may exaggerate inflammation by targeting miR-10a-5p through NF-κB signaling pathway.

Hemophagocytic Lymphohistiocytosis Secondary to Disseminated Talaromyces marneffei and Cytomegalovirus Infections in an HIV-Infected Patient.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening syndrome led by a highly stimulated but invalid immune response, and Talaromyces marneffei (T. marneffei) is an opportunistic infection with high mortality commonly among acquired immunodeficiency syndrome (AIDS) patients. METHODS: Here is a rare case, in which secondary HLH is caused by dual infections of T. marneffei and cytomega-lovirus (CMV). A 15 year old man with a 20-day history of fatigue and intermittent fever (maximum 41.0℃) was admitted to the department of infectious diseases. Marked hepatosplenomegaly and pulmonary infection were detected by computed tomography. Examination of peripheral blood and bone marrow (BM) smears provided clues pointing toward T. marneffei infection, and indicated prominent hemophagocytosis. RESULTS: Cytomegalovirus (CMV) and T. marneffei infections were confirmed by CMV quantitative nucleic acid testing and culture of blood and bone marrow, respectively. A diagnosis of acquired HLH caused by dual infections of T. marneffei and CMV was established because 5 of the 8 HLH diagnostic criteria were met. CONCLUSIONS: The case highlights the contribution of the morphological examination on peripheral blood and bone marrow smears in the diagnosis, which sometimes are the only locations that HLH and T. marneffei can be diagnosed.

Cell signaling pathways based on vitamin C and their application in cancer therapy.

Vitamin C, a small organic molecule, is widely found in fruits and vegetables and is an essential nutrient in the human body. Vitamin C is closely associated with some human diseases such as cancer. Many studies have shown that high doses of vitamin C have anti-tumor ability and can target tumor cells in multiple targets. This review will describe vitamin C absorption and its function in cancer treatment. We will review the cellular signaling pathways associated with vitamin C against tumors depending on the different anti-cancer mechanisms. Based on this, we will further describe some applications of the use of vitamin C for cancer treatment in preclinical and clinical trials and the possible adverse events that can occur. Finally, this review also assesses the prospective advantages of vitamin C in oncology treatment and clinical applications.

Patient with congenital factor VII deficiency undergoing brain tumor neurosurgery successfully treated with recombinant factor VIIa and fresh frozen plasma: A case report and literature review.

RATIONALE: Congenital factor VII deficiency is the most common among rare bleeding disorders, characterized by spontaneous or traumatic bleeding. The clinical manifestation is heterogeneous, ranging from asymptomatic phenotype to life-threatening hemorrhages. Intracranial hemorrhage is a common complication of brain tumor neurosurgery, which significantly challenges the perioperative management of patients with hemostatic defects. PATIENT CONCERNS: This report presented a 55-year-old man with congenital factor VII deficiency, who had no history of hemorrhage or family history. He underwent a craniotomy for the treatment of papillary craniopharyngioma. DIAGNOSES: The patient was diagnosed as papillary craniopharyngioma, factor VII deficiency, and atrial fibrillation. INTERVENTIONS: To prevent bleeding, a total of 8 doses of recombinant activated factor VII and 1 dose of fresh frozen plasma were administered as the perioperative replacement therapy. This scheme was guided by a pharmacodynamic evaluation, laboratory tests, and imaging examinations. OUTCOMES: No excessive surgical bleeding was observed during the 22-day treatment. The patient was found to have compound heterozygous mutations, Ala304Thr (c.910G > A) and IVS5-2A > G (c.572-2A > G), in the F7 gene. LESSONS: This is the first reported case in which surgical hemorrhage secondary to brain tumor resection was successfully controlled in the presence of congenital factor VII deficiency. Perioperative coagulation state, hemostasis, and thrombosis events should be closely observed, and the interval and dosage of recombinant factor VIIa should be adjusted accordingly.

Genetic mutation analysis of hereditary spherocytosis in Guangxi Zhuang Autonomous Region.

Hereditary spherocytosis (HS) is a common, hereditary hemolytic anemia (HHA) that is attributed to the disturbance of five erythrocyte membrane proteins. HS is also common in Guangxi, China. Target region capture high-throughput sequencing technology was used to analyze genetic mutations found in HS patients. Pedigree analysis was also performed, in some cases, to provide an optimized approach for the etiological diagnosis of complex, hereditary hemolytic anemia. Blood samples from the probands and their families were assessed by laboratory tests, target region capture high-throughput sequencing technology, and Sanger sequencing. We detected 79 HS patients from 37 unrelated families. The mutations observed in these patients were found mainly in four HS-related genes. These included SLC4A1, which was mutated in 31.65% of patients (25/79), SPTA1 (30.78% (24/79)), EPB42 (6.33% (5/79)), and SPTB (5.06% (4/79)). Composite genotype was observed in 26.58% (21/79) of patients and included mutations in two or more HS-related genes or mutations in HS-related genes combined with thalassemia or G6PD deficiency. No significant differences in clinical symptoms were found among patients of various genotypes except total bilirubin. Mean reticulocyte volume (MRV) and mean sphered cell volume (MSCV) of the composite genotype were significantly different from other groups. A total of 28 mutation types were found in HS-related genes. Using high-throughput sequencing technology, we also found some cases that had been misdiagnosed. MRV and MSCV are more significant in compound mutations as sensitive determinants of HS. High-throughput sequencing technology can be used to provide a more effective etiological diagnostic method for HS, with high efficiency and specificity.

GLP-1 RA Improves Diabetic Retinopathy by Protecting the Blood-Retinal Barrier through GLP-1R-ROCK-p-MLC Signaling Pathway.

Background: GLP-1 receptor agonists (GLP-1RA) are common clinical agents that are clinically protective against diabetic complications, such as diabetic retinopathy (DR). Previous studies have shown that the RhoA/ROCK pathway plays an important role in the development of DR. However, the specific mechanism of action between GLP-1RA and DR remains unclear. The aim of this study was thus to investigate the main mechanism involved in the protective effect of GLP-1RA on DR. Methods: Type 2 diabetic mice were fed a high-sugar, high-fat diet. Changes in the retinal structure were observed via HE staining and transmission electron microscopy. The expression of retinal GLP-1R, blood-retinal barrier- (BRB-) related proteins, inflammatory factors, and related pathway proteins were studied via Western blot or immunohistochemistry/immunofluorescence analysis. Results: GLP-1RA treatment reduced the blood glucose and lipid levels as well as the body weight of the diabetic mice while also improving retinal thickness, morphology, and vascular ultrastructure. Moreover, restored GLP-1R expression, increased Occludin and ZO-1 levels, and decreased albumin expression led to reduced retinal leakage and improved the BRB by inhibiting the RhoA/ROCK pathway. Conclusions: We found that the protective effect of GLP-1RA on the retina may be realized through the GLP-1R-ROCK-p-MLC signaling pathway.

The prevalence of hyperuricemia and its correlates in Zhuang nationality, Nanning, Guangxi Province.

BACKGROUND: Hyperuricemia has an increasing incidence in various regions year by year, in this study, we evaluated the prevalence of hyperuricemia in a routine physical examination in Nanning, Guangxi Province, and analyzed the influencing factors of hyperuricemia, aiming to provide evidence for the prevention and treatment of hyperuricemia and related diseases. METHODS: Data were collected from 1957 patients who underwent physical examinations at the First Affiliated Hospital of Guangxi Medical University in China since 2017. Questionnaires were structured, including subjects' demographics, lifestyle, personal history, chronic disease history, medication history, etc. UA (uricase method), TC (cholesterol oxidase method), TG (glycerol phosphate oxidase method), HDL-C (direct method), LDL-C (direct method), BUN (rate method), creatinine (sarine oxidase method), and GLU (oxidase-peroxidase method) were detected. Independent risk factors for hyperuricemia were determined by bivariate non-conditional logistic regression analysis. RESULTS: The overall prevalence of hyperuricemia was 16.6% (19.5% in males and 14.9% in females). Gender, waist circumference, BMI, the proportion of drinking, hypertension, high education, serum concentrations of TC, TG, LDL-C, BUN, and creatinine were significantly higher and the serum concentration of HDL-C was significantly lower in patients with and without hyperuricemia (all p < 0.05). Waist circumference, BMI, BUN, and creatinine were independent risk factors for hyperuricemia. CONCLUSION: The prevalence of hyperuricemia is very high in Guangxi. Public health lectures should be conducted to encourage people to establish a healthy lifestyle and strengthen early intervention for hyperuricemia to reduce the risk of cardio-cerebrovascular and other related diseases.

Familial chylomicronemia syndrome caused by compound heterozygous mutation of lipoprotein lipase gene: A case report and review of literature.

Familial chylomicronemia syndrome (FCS) caused by mutations of lipoprotein lipase (LPL) gene and other triglyceride-rich lipoprotein genes related with catabolism is an autosomal recessive rare disease. Herein, we report an infant with FCS and review the relevant literature. The proband is a male infant with FCS for which the whole-exome sequencing (WES), sanger sequencing and copy number variation (CNV) based on WES were performed. Compound heterozygous mutations (LPL gene c.1322+1G>C and loss in exons 8 to 10) were found in the LPL gene of the proband, the c.1322+1G>C mutation was inherited from his father with the heterozygous mutation, and the deletion of exons 8-10 due to CNVs was inherited from his mother. Carriers of heterozygous mutation or heterozygous deletion in LPL may have normal plasma lipids or develop FCS. Plasma lipids management of FCS in infancy should focus on the diet and adopt an individualized management.

Misdiagnosis of a patient with congenital dysfibrinogenemia: A case report and literature review.

BACKGROUND: We reported a patient with congenital dysfibrinogenemia who was misdiagnosed and reviewed relevant literature, in order to discuss the methods to reduce misdiagnosis. METHODS: A 23-year-old pregnant woman was found to be with low fibrinogen in antenatal examination at another province teaching hospital, who was misdiagnosed to have hypofibrinogenemia. Fibrinogen infusion or cryoprecipitation was recommended if necessary. The patient came to our hospital for further diagnosis and treatment considering the safety of herself and the fetus. We examined the coagulation function and gene sequencing of the pregnant woman and her family members. RESULTS: Fibrinogen (Clauss method) was significantly reduced in the patient and her mother, while the level of fibrinogen (PT-derived method) was normal. Thrombin time was prolonged. Heterozygous mutation site was found in exon 2 of the FGA gene, c.104G > A(p.Arg35His). CONCLUSION: When the fibrinogen (Clauss method) is significantly reduced and the thrombin time is prolonged, PT-derived method and the investigation of family coagulation function should be added, which can be used to diagnose and distinguish congenital dysfibrinogenemia from hypofibrinogenemia.