A novel pathogenic mutation in the COL7A1 gene resulting in mild autosomal dominant bullous dermolysis of the newborn

2020 ◽  
Vol 37 (5) ◽  
pp. 955-957
Author(s):  
Michael Lor ◽  
Michael Liu ◽  
Lawrence F. Kuklinski ◽  
Marcia Hogeling
Keyword(s):  
Autosomal Dominant ◽  
Pathogenic Mutation ◽  
Col7a1 Gene

Genetic Linkage Between the Collagen VII (COL7A1) Gene and the Autosomal Dominant Form of Dystrophic Epidermolysis Bullosa in Two Dutch Kindreds

1992 ◽  
Vol 99 (5) ◽  
pp. 528-530 ◽  
Author(s):  
Nelleke A Gruis ◽  
Jan N Bouwes Bavinck ◽  
Peter M Steijlen ◽  
Jan G Van Der Schroeff ◽  
Arie Van Haeringen ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Genetic Linkage ◽  
Autosomal Dominant ◽  
Dominant Form ◽  
Dystrophic Epidermolysis Bullosa ◽  
Autosomal Dominant Form ◽  
Col7a1 Gene ◽  
Collagen Vii

A novel CRYBB2 mutation causes autosomal dominant cataract: A report from a Chinese family

2020 ◽  
pp. 112067212092645
Author(s):  
Li Juan Xu ◽  
Zhi Gang Lv ◽  
Ying Liu ◽  
Xiang Xiang Zhang ◽  
Yu Xin Cui ◽  
...  
Keyword(s):  
Axial Length ◽  
Healthy Subjects ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Rare Mutation ◽  
Pathogenic Variants ◽  
Lens Opacities ◽  
Generation Sequencing

Purpose This study aimed to examine pathogenic mutation within one Chinese family of five-generations suffering from autosomal dominant cataract. Methods Next-generation sequencing and Sanger sequencing were used to find the pathogenic variants. Results A rare mutation, c.563G > A, in CRYBB2 gene was found in the proband that showed symptom of non-syndromic congenital autosomal dominant cataract. This mutation had been found in all affected individuals and in one healthy infant, but it did not exist between two individuals who did not develop such disease in that family, as well as in 100 healthy subjects who showed no relation with that family. Cataracts in this family varied with different severity of lens opacities and elongation of axial length. Conclusion One missense mutation c.563G > A is reported in the CRYBB2 gene among one Chinese family suffering from early-onset cataract, and associated novel phenotypes are the elongation of axial length and the types of cataract. Our results expand the spectrum of associated phenotypes of CRYBB2 mutation.

scholarly journals A Novel GDAP1 Mutation 439delA is Associated with Autosomal Recessive CMT Disease

2006 ◽  
Vol 33 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Domna-Maria Georgiou ◽  
Paschalis Nicolaou ◽  
David Chitayat ◽  
Pantelitsa Koutsou ◽  
Riyana Babul-Hirji ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Molecular Genetic ◽  
Sensory Neuropathy ◽  
Pathogenic Mutation ◽  
Chromosome 8 ◽  
Consanguineous Family ◽  
Single Nucleotide ◽  
The Family ◽  
Neuropathological Criteria

Background:Charcot-Marie-Tooth (CMT) disease is the most common form of inherited motor and sensory neuropathy. Based on neurophysiological and neuropathological criteria CMT has been sub-classified into two main types: demyelinating and axonal. Furthermore, it is genetically heterogeneous with autosomal dominant, autosomal recessive (AR) and X-linked modes of inheritance. Thus far, seven genes have been identified in association with the demyelinating AR-CMT disease. We hereby report our clinical and molecular genetic findings in a consanguineous family with AR-CMT.Methods:Two young sisters with AR-CMT and other non-affected family members were clinically and electrophysiologically evaluated and then molecular genetic investigation was carried out in order to identify the pathogenic mutation.Results:Following an initial indication for linkage of the family to the CMT4A locus on chromosome 8, we sequenced the Ganglioside-induced differentiation-associated protein 1 (GDAP1) gene and identified a single nucleotide deletion in exon 3 that is associated with AR-CMT in the family.Conclusion:We identified a novel GDAP1 439delA mutation that is associated with AR-CMT in a consanguineous family of Iranian descent with two affected young girls and a history in other members of the family.

scholarly journals Clinical and Molecular Characterization of Qatari Patients with Inherited Dysfibrinogenemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1037-1037
Author(s):  
Amna Gameil ◽  
Hajer Al-Mulla ◽  
Aliaa Amer ◽  
Tawfeg Ben-Omran ◽  
Mohamed A Yassin ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Autosomal Dominant ◽  
Clinical Phenotype ◽  
Pathogenic Mutation ◽  
Functional Assay ◽  
Sequencing Analysis ◽  
Thrombin Time ◽  
Whole Exome ◽  
Antigen Assay

Abstract Background and Objectives: Inherited Dysfibrinogenemia is a rare functional fibrinogen disorder in which the fibrinogen protein is present but with a reduced function. Fibrinogen is a 340-kDa glycoprotein that is encoded by three genes namely: Fibrinogen Bb (FGB), Aa (FGA), and g (FGG). The disorder is characterized by a wide spectrum of clinical phenotypes, ranging from asymptomatic to mild- to-severe bleeding or thrombotic manifestations and recurrent miscarriages. The mode of inheritance is mostly autosomal dominant manner and frequently as a result of a point mutation in FGA (Arg35) and FGG (Arg301). The laboratory diagnosis is based on discrepancy between fibrinogen antigen (detected by immunoassay or by immuno-turbidimetric assay) and functional assay (detected by Clauss method or other clot-based assays). The disorder is often associated with prolonged activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT).Fibrinogen activity is reduced by Clauss method while the antigen assay remains normal. The management is directed towards prevention of bleeding with prophylactic fibrinogen concentrates or cryoprecipitate prior to invasive procedures, surgeries or delivery. Dysfibrinogenemia is a rare disorder yet it is very prevalent in Qatar as a result of high rate of consanguineous marriages. The aim of our study is to describe the clinical phenotype in relation to genotype in this cohort. Methods We conducted a retrospective analysis of 23 patients with Inherited Dysfibrinogenemia reported by our center from 2015 to 2020 . Patients with a positive family of history fibrinogen disorder and abnormal coagulation screen, low functional fibrinogen assay (by Clauss method) or normal antigen level by turbidimetry were included. Whole exome sequencing (WES) was performed on the proband case which detected a likely pathogenic mutation that was tested on subsequent cases. We diagnosed our patients with Inherited Dysfibrinogenemia based on both coagulation-based assays and molecular tests. Probable Inherited Dysfibrinogenemia was considered in patients where the molecular test or antigen assay were not performed. To assess the clinical phenotype, data was collected that included; age at diagnosis, gender, bleeding and thrombotic events as well as coagulation screening. (Table 1) Results 23 patients who were described in this cohort belong to the same tribe. 74% (17 o/23) were female and only 41% (7/17) reported an obstetric bleeding (postpartum or post abortion) and one reported mild bleeding that occurred in the postmenopausal period and no previous bleeding (case#19). The median age of diagnosis was 28.8 years (5-69) for the females. All male cases in the cohort were detected either during routine screening or prior to surgery with no previous history of bleeding. No thrombotic events were observed in this cohort. Genetic Analysis Following proper genetic counseling and informed consent, whole exome sequencing analysis (WES) was performed on the index case which included testing of the fibrinogen genes FGA, FGB and FGG. WES revealed a likely pathogenic mutation in the FGA gene (p. Arg35His (R35H) (CGT>CAT): c.104 G>A in exon 2)-Located within the cleavage site of fibrinopeptide A by thrombin (The UniProt Consortium, 2017), which is a mutational hotspot. This result is likely consistent with the diagnosis of Dysfibrinogenemia. Conclusion The FGA R35H mutation is considered a probable recurrent variant in a large tribe in the Qatari population and is associated with late onset mild bleeding manifestations in minority of cases . Despite the fact that the reported tribe is highly consanguineous, the R35H mutation behaved in an autosomal dominant manner rather than recessive in this cohort.Further studies to assess phenotype - genotype correlation of Dysfibrinogenemia is warranted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals A new atypical splice mutation of PKD2 leading to autosomal dominant polycystic kidney disease in a Chinese family

2021 ◽  
Author(s):  
J Zhang ◽  
Y Wang ◽  
Y Zhao ◽  
F Liu
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Pathogenic Mutation ◽  
Chinese Family ◽  
Rt Pcr ◽  
Polycystic Kidney ◽  
Renal Disorder ◽  
Truncating Mutation ◽  
Autosomal Dominant Polycystic Kidney

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a very common hereditary renal disorder. Mutations in PKD1 and PKD2, identified as disease-causing genes, cause about 85% and 15% of ADPKD cases, respectively. Methods: In this study, the mutation analysis of PKD genes was implemented in a Chinese family with suspected ADPKD using targeted clinical exome sequencing (CES). The candidate pathogenic variants were further tested by using Sanger sequencing and validated for co-segregation. In addition, reverse transcription-polymerase chain reaction (RT-PCR) was performed to test abnormal splicing and assess its potential pathogenicity. Results: A novel atypical splicing mutation which belongs to unclassified variants (UCVs), IVS6+5G>C, was identified in three family members by CES and was shown to co-segregate only with the affected individuals. RT-PCR reveals the abnormal splicing of exon 6, thus to cause truncating mutation. These findings suggest that the atypical splice site alteration, IVS6+5G>C, in the PKD2 gene is the potential pathogenic mutation leading to ADPKD in the Chinese family. Conclusion: The data available in this study provided strong evidence that IVS6+5G>C is the potential pathogenic mutation for ADPKD. Meantime, this case also emphasizes the significance of functional analysis of UCVs and genotype-phenotype correlation in ADPKD.

scholarly journals Genetic predictors of survival in behavioral variant frontotemporal degeneration

Neurology ◽  
2019 ◽  
Vol 93 (18) ◽  
pp. e1707-e1714 ◽  
Author(s):  
Carrie Caswell ◽  
Corey T. McMillan ◽  
Sharon X. Xie ◽  
Vivianna M. Van Deerlin ◽  
EunRan Suh ◽  
...  
Keyword(s):  
Symptom Onset ◽  
Autosomal Dominant ◽  
Proportional Hazards ◽  
Age At Onset ◽  
Retrospective Chart Review ◽  
Pathogenic Mutation ◽  
Cox Proportional Hazards ◽  
Frontotemporal Degeneration ◽  
Mutation Status ◽  
Genetic Predictors

ObjectiveTo determine autosomal dominant genetic predictors of survival in individuals with behavioral variant frontotemporal degeneration (bvFTD).MethodsA retrospective chart review of 174 cases with a clinical phenotype of bvFTD but no associated elementary neurologic features was performed, with diagnosis either autopsy-confirmed (n = 57) or supported by CSF evidence of non-Alzheimer pathology (n = 117). Genetic analysis of the 3 most common genes with pathogenic autosomal dominant mutations associated with frontotemporal degeneration was performed in all patients, which identified cases with C9orf72 expansion (n = 28), progranulin (GRN) mutation (n = 12), and microtubule-associated protein tau (MAPT) mutation (n = 10). Cox proportional hazards regressions were used to test for associations between survival and mutation status, sex, age at symptom onset, and education.ResultsAcross all patients with bvFTD, the presence of a disease-associated pathogenic mutation was associated with shortened survival (hazard ratio [HR] 2.164, 95% confidence interval [CI] 1.391, 3.368). In separate models, a GRN mutation (HR 2.423, 95% CI 1.237, 4.744), MAPT mutation (HR 8.056, 95% CI 2.938, 22.092), and C9orf72 expansion (HR 1.832, 95% CI 1.034, 3.244) were each individually associated with shorter survival relative to sporadic bvFTD. A mutation on the MAPT gene results in an earlier age at onset than a C9orf72 expansion or mutation on the GRN gene (p = 0.016).ConclusionsOur findings suggest that autosomal dominantly inherited mutations, modulated by age at symptom onset, associate with shorter survival among patients with bvFTD. We suggest that clinical trials and clinical management should consider mutation status and age at onset when evaluating disease progression.

Expression of normal sequence pathogenic proteins for neurodegenerative disease contributes to disease risk: ‘permissive templating’ as a general mechanism underlying neurodegeneration

2005 ◽  
Vol 33 (4) ◽  
pp. 578-581 ◽  
Author(s):  
J. Hardy
Keyword(s):  
Neurodegenerative Disease ◽  
Autosomal Dominant ◽  
Disease Risk ◽  
Deposition Process ◽  
Pathogenic Mutation ◽  
General Mechanism ◽  
Key Factor ◽  
Dominant Disease ◽  
Jakob Disease ◽  
Two Stages

Loci underlying autosomal dominant forms of most neurodegenerative disease have been identified: prion mutations cause Gerstmann Straussler syndrome and hereditary Creutzfeldt–Jakob disease, tau mutations cause autosomal dominant frontal temporal dementia and α-synuclein mutations cause autosomal dominant Parkinson's disease. In these cases, the pathogenic mutation is in the protein that is deposited in the diseased tissue and the whole protein is deposited. In Alzheimer's disease, mutations in amyloid precursor protein or in the presenilins cause autosomal dominant disease. These are the substrate and proteases responsible for the production of the deposited peptide Aβ. Thus, in all the cases, the mutations lead to the disease by a mechanism that involves the deposition process. Furthermore, sporadic forms of all these diseases are predisposed by genetic variability at the same loci, implying that the quantity of the normal protein influences the risk of this form of disease. These results show that the amount of pathogenic protein expression is a key factor in determining disease initiation. Recent work on transgenic models of these diseases is consistent with the view that there are two stages of pathogenesis: a concentration-dependent formation of a pathogenic protein oligomer followed by aggregation on to this oligomeric template by a process that is less dependent on the concentration of the protein.

scholarly journals Autosomal dominant mutation in COL7A1 gene causing epidermolysis bullosa dystrophica

2014 ◽  
Vol 7 (Suppl 1) ◽  
pp. P58 ◽  
Author(s):  
Jayesh Sheth ◽  
Mehul Mistri ◽  
Harsh Patel ◽  
Chitra Ankleshwaria ◽  
Aradhana Parikh
Keyword(s):  
Epidermolysis Bullosa ◽  
Autosomal Dominant ◽  
Dominant Mutation ◽  
Epidermolysis Bullosa Dystrophica ◽  
Col7a1 Gene
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