scholarly journals A review of multi-dimensional diagnosis of Alport syndrome in 22 children in Northeast China

2020 ◽  
Author(s):  
Li Zhang ◽  
Bai-chao Sun ◽  
Bing-gang Zhao ◽  
Qing-shan Ma
Keyword(s):  
Alport Syndrome ◽  
Age Of Onset ◽  
Pediatric Nephrology ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Basement Membranes ◽  
Economic Factors ◽  
Visual Problem ◽  
Risk Of Progression ◽  
Dimensional Diagnosis

Abstract Background Alport syndrome (AS) is progressive hereditary nephritis due to different gene mutations. Affected individuals usually develop hematuria during childhood with gradual deterioration of renal functions. We adopted multi-dimensional methods to diagnose Alport syndrome in order to decrease the misdiagnosis.Methods Twenty-two children were diagnosed and managed by the Department of Pediatric Nephrology of Jilin University First Hospital between January 2017 and January 2020 through multi-dimensional methods. Information collected included age of onset, age at diagnosis, clinical manifestations, family history (FH), renal pathology and their genotype. Results All patients presented with hematuria with various degrees of proteinuria in some patients. While three children suffered from hearing loss, none of the children in the cohort had any visual problem or renal failure. Besides five patients estimated as Stage 2, the remain seventeen cases were at Stage 0. Renal biopsy were obtained in eighteen patients and fourteen of them showed glomerular basement membranes (GBM)-specific abnormalities. Thirteen children had mutations of the collagen IV genes. Conclusion Combined with the importance of early diagnosis and economic factors, we adopted multi-dimensional methods to improve the diagnosis of Alport syndrome and estimate the risk of progression. We also reviewed the therapy progress.

scholarly journals A Review of Multi-dimensional Diagnosis of Alport Syndrome in 22 Children in Northeast China

2020 ◽  
Author(s):  
Li Zhang ◽  
Bai-chao Sun ◽  
Bing-gang Zhao ◽  
Qing-shan Ma
Keyword(s):  
Alport Syndrome ◽  
Age Of Onset ◽  
Pediatric Nephrology ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Basement Membranes ◽  
Economic Factors ◽  
Visual Problem ◽  
Risk Of Progression ◽  
Dimensional Diagnosis

Abstract Background Alport syndrome (AS) is progressive hereditary nephritis due to different gene mutations. Affected individuals usually develop hematuria during childhood with gradual deterioration of renal functions. We adopted multi-dimensional methods to diagnose Alport syndrome in order to decrease the misdiagnosis.Methods Twenty-two children were diagnosed and managed by the Department of Pediatric Nephrology of Jilin University First Hospital between January 2017 and January 2020 through multi-dimensional methods. Information collected included age of onset, age at diagnosis, clinical manifestations, family history (FH), renal pathology and their genotype. Results All patients presented with hematuria with various degrees of proteinuria in partial patients. While three children suffered from hearing loss, none of the children in the cohort had any visual problem or renal failure. Besides five patients estimated as Stage 2, the remain seventeen cases were at Stage 0. Renal biopsy were obtained in eighteen patients and fourteen of them showed glomerular basement membranes (GBM)-specific abnormalities. Thirteen children had mutations of the collagen IV genes.Conclusion Combined with the importance of early diagnosis and economic factors, we adopted multi-dimensional methods to diagnose Alport syndrome and estimate the risk of progression. We also reviewed the therapy progress.

Alport Syndrome: a comprehensive review on genetics, pathophysiology, histology, clinical, and therapeutic perspectives

2021 ◽  
Vol 28 ◽  
Author(s):  
Ana Luisa Pedrosa ◽  
Letícia Bitencourt ◽  
Rafaela Moreira Paranhos ◽  
Cristiana Afonso Leitão ◽  
Guilherme Costa Ferreira ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
De Novo ◽  
Lysyl Oxidase ◽  
Clinical Investigation ◽  
Clinical Manifestations ◽  
Basement Membranes ◽  
De Novo Mutations ◽  
Vascular Abnormalities ◽  
Wide Range ◽  
Novel Therapeutic

Background: Alport syndrome (AS) is a disease caused by mutations in COL4A3, COL4A4 or COL4A5, the genes that encode distinct chains of type IV collagen. The vast majority of cases presents as an inherited disorder, although de novo mutations are present in around 10% of the cases. Methods: This non-systematic review summarizes recent evidence on AS. We discuss the genetic and pathophysiology of AS, clinical manifestations, histopathology, diagnostic protocols, conventional treatment and prognostic markers of the disease. In addition, we summarize experimental findings with novel therapeutic perspectives for AS. Results: The deficient synthesis of collagen heterotrimers throughout the organism leads to impaired basement membranes (BM) in several organs. As a result, the disease manifests in a wide range of conditions, particularly renal, ocular and auricular alterations. Moreover, leiomyomatosis and vascular abnormalities may also be present as atypical presentations. In this framework, diagnosis can be performed based on clinical evaluation, skin or renal biopsy and genetic screening, the latter being the gold standard. There are no formally approved treatments for AS, even though therapeutic options have been described to delay disease progression and increase life expectancy. Novel therapeutic targets under pre-clinical investigation included paricalcitol, sodium-glucose co-transporter-2 inhibitors, bardoxolone methyl, anti-microRNA-21 oligonucleotides, recombinant human pentraxin-2, lysyl oxidase-like-2 blockers, hydroxypropyl-b-cyclodextrin, sodium 4- phenylbutyrate and stem cell therapy. Conclusion: AS is still a greatly under and misdiagnosed disorder. The pathophysiology is still not fully unnderstand and genetics of the disease have also some gaps. Up to know, there is no specific and effective treatment for AS. Further studies are necessary to establish novel and effective therapeutic protocols.

scholarly journals Application of High-Throughput Sequencing in the Diagnosis of Inherited Immune-Thrombocytopenia from Children Chronic/Refractory ITP

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 86-86
Author(s):  
Ma Jingyao ◽  
Zhenping Chen ◽  
Huiqing LIU ◽  
Jialu Zhang ◽  
Hao GU ◽  
...  
Keyword(s):  
Platelet Count ◽  
High Throughput ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Age Of Onset ◽  
Prognostic Significance ◽  
Genetic Diagnosis ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Refractory Itp

BACKGROUND: Inherited thrombocytopenias are a group of hereditary diseases with reduced platelet counts and associated bruising and bleeding as the main clinical manifestations. These entities may be hard to distinguish from ITP, particularly difficult immune thrombocytopenia complicates primary immunodeficiency and immunological treatments are effective in increasing the platelet count. Then when the course of thrombocytopenia is prolonged and other abnormalities, eg. infection, either are non-existent or subtle, distinguishing such diseases from ITP may be clinically almost impossible. However, in order to carry out proper disease management, accurate diagnosis is very necessary and urgently needed, especially in childhood. OBJECTIVES: To evaluate: 1) the detection rate of inherited immune thrombocytopenia by high-throughput, next-generation sequencing (NGS) from children with apparent chronic and refractory ITP, and 2) the value of NGS in screening and diagnosis of inherited "immune" thrombocytopenia. METHODS: We retrospectively collected 245 cases of chronic and refractory ITP in children with transient response to Intravenous Immunoglobulin (IVIG) and/ or glucocorticoid and/ or other immunosuppressive therapy, all of whom underwent genetic testing from April 2016 to April 2019. Their clinical data were systematically recorded and analyzed. We introduced a high-throughput, NGS platform into the routing diagnosis of those patients and analyzed the gene-sequencing results. We compared the differences between patients with positive gene mutations and those who carried suspected gene mutations. All subjects and their legal guardians gave written informed consent to the investigation. RESULTS: Sixteen patients were excluded as their final diagnosis was malignancy, aplastic anemia (AA), or myelodysplastic syndrome (MDS). Among the remaining 229 cases, 32 patients (14%) received a genetic diagnosis. Twenty-five patients (11%) had pathogenic mutations in 12 genes including CASP10(2), WAS(12), LRBA(1), CARD(1), ITGA2B(2), ITGB(1), CD36(1), NFKB2(1), NBEAL2(1), UNC13D(1), KMT2D(1), TNFRS13B(1) known to be included in lymphoproliferation or autoimmunity, whereas 7 patients (3%) carried a suspected pathogenic variant in 6 genes including: GATA(1), MYH-9(1), PTPN-11(1), RUNX(1), SLX4(2), TUBB1(1) that had not been reported in the context of autoimmune diseases. Among the 25 patients with known mutations, 16 patients (7%) could be definitely diagnosed as inherited immune thrombocytopenia and formed the Diagnosed Group (DG) according to their phenotype, inheritance and pathogenicity of the mutated gene, while 9 cases in this category and 7 patients who carried probable pathogenic variants constitute the Suspected Diagnosed Group (SDG). We compared their clinical and laboratory phenotype with the biggest difference identified in age of onset (median: 4.08 months in DG vs 54.00 months in SDG, P =0.002). Other variables analyzed included duration of time with misdiagnosis (median: 13.5 months vs 26.0 months, P=0.430), baseline platelet count (median: 6×109/L vs 5×109/L, P=.0.282), level of IL-4 (median: 0 vs 0, P=0.232), level of IL-6 (median: 13.32 vs 7.48 P=1.000), bleeding severity (without any bleeding: 1 vs 0; merely petechia/ecchymosis: 3 vs 6; bleeding in skin and one another location: 6 vs 4; bleeding in more than 2 location: 2 vs 2. P=0.542) and rate of identification of autoimmune antibodies between the two groups (P=0.662). CONCLUSIONS: Definite or suspected genetic etiologies consistent with inherited immune thrombocytopenia were identified in approximately one-seventh of cases of apparent chronic ITP. These cases would have been classified as "routine" cases of childhood ITP based on response to standard first-line ITP treatments and the absence of overt other findings. Eventually, their chronicity would have increased suspicion of an underlying etiology and the correct diagnosis made. The definite diagnosis group and the suspected group were identical clinically and in laboratory testing in every way except for age of onset suggesting that the suspected group was also likely inherited immune thrombocytopenia. Wide-ranging genetic screening (NGS) should be offered in children chronic/refractory ITP. The genetic findings have prognostic significance and may guide the choice of a targeted treatment in the future. Disclosures No relevant conflicts of interest to declare.

scholarly journals MODERN PROBLEMS OF АLPORT SYNDROME DIAGNOSIS

2020 ◽  
Vol 25 ◽  
pp. 21-25
Author(s):  
Olena Bratnova
Keyword(s):  
Family History ◽  
Alport Syndrome ◽  
Kidney Biopsy ◽  
Clinical Manifestations ◽  
Basement Membranes ◽  
Diagnostic Methods ◽  
Collagen Type Iv ◽  
Educational Work ◽  
Type Iv ◽  
Analysis And Synthesis

Introduction. In the practice of adult nephrologists there are cases of rare genetically caused kidney damage, in particular, Alport syndrome. This is due to the availability and improvement of instrumental diagnostic methods, timely approaches to treatment in pediatric practice, and prolongation of the pre-dialysis period. Goal. Analysis and synthesis of new data from domestic and foreign sources on the etiology, pathogenesis, clinical manifestations, types of inheritance, differential diagnosis of Alport syndrome in order to improve the success of students, interns and teachers in the study of nephrological subjects. Material and methods. Review of contemporary and foreign literary sources; techniques – description, analysis, abstracting. Results. Alport syndrome (AS, synonym: hereditary nephritis) is non-immune genetically determined glomerulopathy caused by a mutation of genes that encode collagen type IV of basement membranes, manifested by hematuria and / or proteinuria, a progressive decreased renal function, combined with pathology of hearing and abnormalities affecting the eyes. Alport syndrome inherited type: X-linked dominant (XLAS): 85%, autosomal recessive (ARAS): 15%, autosomal dominant (ADAS): 1%. Conclusions. Family history, electron microscopy, immunochemical analysis of type IV collagen expression are informative for verifying the diagnosis of Alport syndrome. Due to the rarity of this disease, in addition, the fact that patients often refuse kidney biopsy, it is necessary to cooperate more closely with genetic laboratories, to take measures to improve the availability of molecular analysis of mutations of collagen IV genes. In addition, it is a fact that sometimes the family history of the disease is ambiguous, unavailable for genetic analysis, and patients refuse to have a kidney biopsy. It is a motive to encourage doctors to improve their educational work with patients about safety of this analysis and its value.

scholarly journals Idiopathic CRMO and MEFV Gene Variant Alleles: Is There Any Relationship?

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Farhad Salehzadeh ◽  
Hassan Anari ◽  
Sepehr Sarkhanloo
Keyword(s):  
Age Of Onset ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Bone Lesions ◽  
Gene Variant ◽  
Intermittent Fever ◽  
Pathogenic Variants ◽  
Long Duration ◽  
Variant Alleles

Background and Objective. CRMO is an inflammatory disease of bone that occurs more often in children. The clinical manifestations are intermittent fever, pain, and bone lesions, especially in long bones. Although there is an idiopathic type of disease, it is usually associated with some autoimmune disorders. This study evaluates MEFV gene mutations as background pathology of idiopathic CRMO. Methods. Blood samples of patients, who diagnosed as childhood idiopathic CRMO by imaging and pathologic study from June 2011 until September 2018, have been screened for the 12 common pathogenic variants of MEFV gene mutations. Result. Nine patients enrolled in this study, and eight of them were male. The most common involvement locations were tibia and femur, and the least ones were zygoma, calcaneus, and radius. The mean duration of the involvement was 1.3 years. Six patients had only 1 involved location, 2 patients showed two sites of involvement, and one patient had three affected areas. There were two positive MEFV gene mutations (22%), as E148Q/wt and K695R/wt both in the heterozygote form. There was no meaningful relationship between MEFV gene mutations and the age of onset, gender, and location of involvement. Patients with positive mutation had more involved sites and long duration of involvement significantly. Conclusion. There is no significant immunopathogenic relationship between the common MEFV gene variant alleles and CRMO disease.

A glance on dystonias, how to recognize and handle them

2019 ◽  
pp. 22-29
Author(s):  
F. N. Mercan ◽  
E. Bayram ◽  
M. C. Akbostanci
Keyword(s):  
Differential Diagnosis ◽  
Movement Disorder ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Body Part ◽  
Classification Model ◽  
Treatment Choices ◽  
Muscle Groups

Dystonia refers to an involuntary, repetitive, sustained, painful and twisting movements of the affected body part. This movement disorder was first described in 1911 by Hermain Oppenheim, and many studies have been conducted to understand the mechanism, the diagnosis and the treatment of dystonia ever since. However, there are still many unexplained aspects of this phenomenon. Dystonia is diagnosed by clinical manifestations, and various classifications are recommended for the diagnosis and the treatment. Anatomic classification, which is based on the muscle groups involved, is the most helpful classification model to plan the course of the treatment. Dystonias can also be classified based on the age of onset and the cause. These dystonic syndromes can be present without an identified etiology or they can be clinical manifestations of a neurodegenerative or neurometabolic disease. In this review we summarized the differential diagnosis, definition, classifications, possible mechanisms and treatment choices of dystonia.

Adult systemic lupus erythematosus in Egypt: The nation-wide spectrum of 3661 patients and world-wide standpoint

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Tamer A Gheita ◽  
Rasha Abdel Noor ◽  
Esam Abualfadl ◽  
Osama S Abousehly ◽  
Iman I El-Gazzar ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Age Of Onset ◽  
Wide Spectrum ◽  
Age At Onset ◽  
Disease Onset ◽  
Clinical Manifestations ◽  
Population Based ◽  
Systemic Lupus ◽  
Cross Sectional

Objective The aim of this study was to present the epidemiology, clinical manifestations and treatment pattern of systemic lupus erythematosus (SLE) in Egyptian patients over the country and compare the findings to large cohorts worldwide. Objectives were extended to focus on the age at onset and gender driven influence on the disease characteristics. Patients and method This population-based, multicenter, cross-sectional study included 3661 adult SLE patients from Egyptian rheumatology departments across the nation. Demographic, clinical, and therapeutic data were assessed for all patients. Results The study included 3661 patients; 3296 females and 365 males (9.03:1) and the median age was 30 years (17–79 years), disease duration 4 years (0–75 years) while the median age at disease onset was 25 years (4–75 years). The overall estimated prevalence of adult SLE in Egypt was 6.1/100,000 population (1.2/100,000 males and 11.3/100,000 females).There were 316 (8.6%) juvenile-onset (Jo-SLE) and 3345 adult-onset (Ao-SLE). Age at onset was highest in South and lowest in Cairo (p < 0.0001). Conclusion SLE in Egypt had a wide variety of clinical and immunological manifestations, with some similarities with that in other nations and differences within the same country. The clinical characteristics, autoantibodies and comorbidities are comparable between Ao-SLE and Jo-SLE. The frequency of various clinical and immunological manifestations varied between gender. Additional studies are needed to determine the underlying factors contributing to gender and age of onset differences.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

scholarly journals Prevalence and clinical phenotype of the triplicated α-globin genes and its ethnic and geographical distribution in Guizhou of China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xi Luo ◽  
Xiang-mei Zhang ◽  
Liu-song Wu ◽  
Jindong Chen ◽  
Yan Chen
Keyword(s):  
Genetic Counseling ◽  
Peripheral Blood ◽  
Clinical Phenotype ◽  
Globin Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Guizhou Province ◽  
Globin Genes ◽  
Phenotype Correlation ◽  
Chi Square

Abstract Background α-thalassemia is relatively endemic in Guizhou province of southwestern China. To predict the clinical manifestations of α-globin gene aberration for genetic counseling, we examined the prevalence of the α-globin triplication and the genotype–phenotype correlation in this subpopulation Methods A cohort of 7644 subjects was selected from nine ethnicities covering four regions in Guizhou province of China. Peripheral blood was collected from each participant for routine blood testing and hemoglobin electrophoresis. PCR-DNA sequencing and Gap-PCR were used to identify the thalassemia gene mutations. Chi-square tests and one-way analysis of variance (ANOVA) were used to statistically analyze the data. Results We found that the frequency of α-globin triplication in Guizhou province was 0.772% (59/7644). Genotypically, the αααanti4.2/αα accounted for 0.523% (40/7644), the αααanti3.7/αα for 0.235% (18/7644), and the αααanti3.7/–SEA for 0.013% (1/7644). The αααanti4.2/αα is more prevalent than the αααanti3.7/αα in Guizhou. In addition, the frequency of the HKαα/αα (that by GAP-PCR is like αααanti4.2/-α3.7) was 0.235% (18/7644). Ethnically, the Tujia group presented the highest prevalence (2.47%) of α-globin triplication. Geographically, the highest frequency of the α-globin triplication was identified in Qiannan region (2.23%). Of the triplicated α-globin cases, 5 coinherited with heterozygote β-thalassemia and presented various clinical manifestations of anemia. Conclusions These data will be used to update the Chinese triplicated α-globin thalassemia database and provide insights into the pathogenesis of thalassemia. These findings will be helpful for the diagnosis of thalassemia and future genetic counseling in those regions.

Mucolipidosis Type IV: Clinical Spectrum and Natural History

PEDIATRICS ◽  
1987 ◽  
Vol 79 (6) ◽  
pp. 953-959
Author(s):  
Naomi Amir ◽  
Joel Zlotogora ◽  
Gideon Bach
Keyword(s):  
Age Of Onset ◽  
Clinical Manifestations ◽  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
First Year Of Life ◽  
Developmental Features ◽  
Mucolipidosis Type

The clinical spectrum and developmental features of mucolipidosis type IV, a recessive lysosomal storage disorder, are presented. The evaluation was based on information from the clinical charts and information obtained from the families of 20 patients between the ages of 2 to 17 years. The clinical manifestations of the disease, profound psychomotor retardation and visual impairment, appear during the first year of life. Definitive diagnosis is made by electron microscopy which reveals storage organelles typical of the mucolipidoses. This study details, for the first time, the heterogeneity of the ophthalmologic features, specifically as pertains to the age of onset, degree and clinical course of the corneal opacities, and the retinal involvement. Although the top developmental level was found to be 12 to 15 months in language and motor function, the course of the disease is protracted for some children, who show only a slight improvement, and others, little if any deterioration despite the early infantile onset of the disease. This presentation provides guidelines for the clinical diagnosis of mucolipidosis type IV.

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