BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which ...BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.展开更多
BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ syste...BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ systems;however,it frequently occurs in the lungs accompanied with unexplained pleural effusion.Further,it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities.However,after birth the newborn rapidly develops respiratory distress that quickly deteriorates.Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease.We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes,which have not been reported previously.CASE SUMMARY We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth.An autopsy revealed lymphangiectasia of the organ systems.Further,whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes,ADAMTS3 and FLT4,and Sanger verification revealed similar lesions in the mother with no symptoms.CONCLUSION Considering the presented case,obstetricians should observe unexplained foetal pleural effusion,and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.展开更多
Matrix metalloproteinases (MMPs) are a family of extracellular proteases capable of degrading various proteinaceous components of the extracellular matrix (ECM).They have been implicated to play important roles in a n...Matrix metalloproteinases (MMPs) are a family of extracellular proteases capable of degrading various proteinaceous components of the extracellular matrix (ECM).They have been implicated to play important roles in a number of developmental and pathological processes, such as tumor metastasis and inflammation. Relatively few studies have been carried out to investigate the function of MMPs during postembryonic organ-development. Using Xenopus laevis development as a model system, we demonstrate here that three MMPs, stromelysin-3 (ST3),collagenases-3 (Col3), and Col4, have distinct spatial and temporal expression profiles during metamorphosis as the tadpole transforms into a frog. In situ hybridizations reveal a tight, but distinct, association of individual MMPs with tissue remodeling in the tail and intestine during metamorphosis. In particular, ST3 expression is strongly correlated with apoptosis in both organs as demonstrated by analyses of serial sections with in situ hybridization for ST3 mRNA and TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling) for apoptosis, respectively. On the other hand, Col3 and Col4 MMPs in Xenopus laevis development are present in regions where extensive connective tissue remodeling take place. These results indicate that ST3 is likely to play a role in ECM-remodeling that facilitateapoptotic tissue remodeling or resorption while Col3 and Col4 appear to participate in connective tissue degradation during development.展开更多
BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused ...BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.展开更多
The effect of repressors on ion channel gene expression was studied. The hKv4. 3 promoter and the sequence （ ＋ 2-- ＋ 160, S160） of 5＇-UTR of the hKv4. 3 gene was cloned into the pβ-gal-Basic vector. The transien...The effect of repressors on ion channel gene expression was studied. The hKv4. 3 promoter and the sequence （ ＋ 2-- ＋ 160, S160） of 5＇-UTR of the hKv4. 3 gene was cloned into the pβ-gal-Basic vector. The transient expression of the pβ-gal vector and the analysis of the relative activity of β-galactosidase were carried out. The analysis of the mRNA level was carried out with the RT-PCR method. S160 could intensively repress the expression of the hKv4. 3 gene with position-specificity. The level of mRNA did not alter obviously. A repressor（ S160）, in 5＇-UTR of the hKv4. 3 gene was found and its repression to gene expression may play a role in the post-transcription process.展开更多
Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This...Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This experiment explored the relationship between NKX2-5,GATA4 and ZIC3 gene mutations and sporadic CHD in Hainan Province.Methods:To collect 210 sporadic CHD patients in Hainan,the DNA of patients was extracted from blood,and the target gene fragments were amplified.Using high-resolution melting(HRM)and DNA sequencing technology,and we analyzed the sequences of NKX2-5,GATA4 and ZIC3 genes.Results:NKX2-5,GATA4 and ZIC3 genes were sequenced in 210 CHD patients,and seven gene mutations were found,including NKX2-5 heterozygous missense mutation(c.178G>T)and three heterozygous mutations in GATA4(c.677C>T,c.928A>G,c.1123G>A),three heterozygous mutations in ZIC3(c.19G>C,c.1255C>G,c.1348C>T),in which NKX2-5(c.178G>T),GATA4(c.1123G>A),and ZIC3(c.1255C>G,c.1348C>T)are new mutation sites.These gene mutations were predicted to be pathogenic mutations by bioinformatics software.Conclusion:Conclusion:Seven gene mutations were found in 210 patients,and it was the first report that the gene mutations of NKX2-5,GATA4 and ZIC3 in Hainan Province associated with the pathogenesis of CHD.展开更多
基金Supported by The Major Project of Zhejiang Administration of Traditional Chinese Medicine,No.2020ZZ008.
文摘BACKGROUND Alport syndrome(AS)is an inherited disease of the glomerular basement membrane caused by mutations in genes encodingα3,α4,orα5 chains of type IV collagen.It manifests with hematuria or proteinuria,which is often accompanied by hearing impairments and ocular abnormalities.Histopathologically,AS shows mesangial proliferation and sometimes incidental immunoglobulin A(IgA)deposition.Hematuria or proteinuria is also a common presentation in patients with IgA nephropathy that makes it difficult to differentially diagnose AS and IgA nephropathy solely based on these clinical and pathological features.CASE SUMMARY Herein,we present the case of a 59-year-old female patient who was admitted to our hospital with persistent microscopic hematuria and occasional proteinuria that had lasted for>2 years.This patient had a familial history of renal disease and was diagnosed with autosomal dominant AS(ADAS)and IgA nephropathy based on the findings of renal biopsy as well as genetic testing performed using whole-exome sequencing,which suggested that the patient carried a novel heterozygous variation(c.888G>A:p.Gln296Gln)in the COL4A3 gene that enriches the mutation spectrum of ADAS.The proband received an angiotensin receptor blocker therapy after a definitive diagnosis was established.After one year of therapy,a significant reduction in proteinuria was observed.The number of microscopic red blood cells per high-power field decreased to one-quarter of the baseline levels.Renal function also maintained well during the follow-up.CONCLUSION Our case highlights the significance of performing kidney biopsy and genetic testing in the diagnosis of AS and familial IgA nephropathy.
基金The Wu Jieping Medical Foundation Clinical Research Special Grant Fund in China,No.320.6750.2022-15-9.
文摘BACKGROUND Congenital lymphangiectasia is a rare disease characterized by dilated interstitial lymphatic vessels and cystic expansion of the lymphatic vessels.Congenital lymphangiectasia can affect various organ systems;however,it frequently occurs in the lungs accompanied with unexplained pleural effusion.Further,it might not be diagnosed during prenatal examination owing to the absence of pronounced abnormalities.However,after birth the newborn rapidly develops respiratory distress that quickly deteriorates.Genetic variations in proteins controlling the development of lymphatic vessels contribute to the pathophysiology of this disease.We report a rare case of heterozygous mutation of ADAMTS3 and FLT4 genes,which have not been reported previously.CASE SUMMARY We analysed the case of a neonate who had presented with only pleural effusion at a late gestational age and eventually died due to its inability to establish spontaneous breathing after birth.An autopsy revealed lymphangiectasia of the organ systems.Further,whole exome sequencing revealed heterozygous mutations of the lymphangiogenesis-controlling genes,ADAMTS3 and FLT4,and Sanger verification revealed similar lesions in the mother with no symptoms.CONCLUSION Considering the presented case,obstetricians should observe unexplained foetal pleural effusion,and perform pathology analysis and whole exome sequencing for a conclusive diagnosis and prompt treatment.
文摘Matrix metalloproteinases (MMPs) are a family of extracellular proteases capable of degrading various proteinaceous components of the extracellular matrix (ECM).They have been implicated to play important roles in a number of developmental and pathological processes, such as tumor metastasis and inflammation. Relatively few studies have been carried out to investigate the function of MMPs during postembryonic organ-development. Using Xenopus laevis development as a model system, we demonstrate here that three MMPs, stromelysin-3 (ST3),collagenases-3 (Col3), and Col4, have distinct spatial and temporal expression profiles during metamorphosis as the tadpole transforms into a frog. In situ hybridizations reveal a tight, but distinct, association of individual MMPs with tissue remodeling in the tail and intestine during metamorphosis. In particular, ST3 expression is strongly correlated with apoptosis in both organs as demonstrated by analyses of serial sections with in situ hybridization for ST3 mRNA and TUNEL (terminal deoxyribonucleotidyl transferase-mediated dUTP-biotin nick end labeling) for apoptosis, respectively. On the other hand, Col3 and Col4 MMPs in Xenopus laevis development are present in regions where extensive connective tissue remodeling take place. These results indicate that ST3 is likely to play a role in ECM-remodeling that facilitateapoptotic tissue remodeling or resorption while Col3 and Col4 appear to participate in connective tissue degradation during development.
基金Supported by The Department of Science and Technology of Guizhou Province,No.[2020]1Y299National Natural Science Foundation of China,No.82060123+2 种基金National Health Commission of Guizhou Province,No.gzwjk2019-1-082Doctor Start Fund of Affiliated Hospital of Guizhou Medical University,No.gyfybsky-2021-28National Natural Cultivation Fund of Affiliated Hospital of Guizhou Medical University,No.Ⅰ-2020-12.
文摘BACKGROUND Gene mutations in ATP-binding cassette,subfamily B(ABCB4)lead to autosomal recessive disorders.Primary light amyloidosis is a rare and incurable disease.Here,we report a rare case of liver cirrhosis caused by ABCB4 gene mutation combined with primary light amyloidosis.CASE SUMMARY We report a case of a 25-year-old female who was hospitalized due to recurrent abdominal pain caused by calculous cholecystitis and underwent cholecystectomy.Pathological examination of the liver tissue suggested liver cirrhosis with bile duct injury.Exon analyses of the whole genome from the patient’s peripheral blood revealed the presence of a heterozygous mutation in the ABCB4 gene.Bone marrow biopsy tissues,renal puncture examination,and liver mass spectrometry confirmed the diagnosis of a rare progressive familial intrahepatic cholestasis type 3 with systemic light chain type κ amyloidosis,which resulted in cirrhosis.Ursodeoxycholic acid and the cluster of differentiation 38 monoclonal antibody daretozumab were administered for treatment.Following treatment,the patient demonstrated significant improvement.Urinary protein became negative,peripheral blood-free light chain and urine-free light chain levels returned to normal,and the electrocardiogram showed no abnormalities.Additionally,the patient’s lower limb numbness resolved,and her condition remained stable.CONCLUSION This report presents the diagnosis and treatment of liver cirrhosis,a rare disease that is easily misdiagnosed or missed.
文摘The effect of repressors on ion channel gene expression was studied. The hKv4. 3 promoter and the sequence （ ＋ 2-- ＋ 160, S160） of 5＇-UTR of the hKv4. 3 gene was cloned into the pβ-gal-Basic vector. The transient expression of the pβ-gal vector and the analysis of the relative activity of β-galactosidase were carried out. The analysis of the mRNA level was carried out with the RT-PCR method. S160 could intensively repress the expression of the hKv4. 3 gene with position-specificity. The level of mRNA did not alter obviously. A repressor（ S160）, in 5＇-UTR of the hKv4. 3 gene was found and its repression to gene expression may play a role in the post-transcription process.
基金Natural Science Foundation of Hainan Province(No.821RC562)Re-research Project of Hainan Province(No.ZDYF2022SHF2081)+1 种基金National Natural Science Foundation of China(No.81660224)Graduate Innovation Project of Hainan Province(No.Qhys2021-353)。
文摘Objective:Congenital heart disease(CHD)is caused by abnormal cardiac development,which is the most common congenital malformation at home and abroad.NKX2-5,GATA4 and ZIC3 have been shown to be associated with CHD.This experiment explored the relationship between NKX2-5,GATA4 and ZIC3 gene mutations and sporadic CHD in Hainan Province.Methods:To collect 210 sporadic CHD patients in Hainan,the DNA of patients was extracted from blood,and the target gene fragments were amplified.Using high-resolution melting(HRM)and DNA sequencing technology,and we analyzed the sequences of NKX2-5,GATA4 and ZIC3 genes.Results:NKX2-5,GATA4 and ZIC3 genes were sequenced in 210 CHD patients,and seven gene mutations were found,including NKX2-5 heterozygous missense mutation(c.178G>T)and three heterozygous mutations in GATA4(c.677C>T,c.928A>G,c.1123G>A),three heterozygous mutations in ZIC3(c.19G>C,c.1255C>G,c.1348C>T),in which NKX2-5(c.178G>T),GATA4(c.1123G>A),and ZIC3(c.1255C>G,c.1348C>T)are new mutation sites.These gene mutations were predicted to be pathogenic mutations by bioinformatics software.Conclusion:Conclusion:Seven gene mutations were found in 210 patients,and it was the first report that the gene mutations of NKX2-5,GATA4 and ZIC3 in Hainan Province associated with the pathogenesis of CHD.
