scholarly journals Phenotypic and Genotypic Characterization of DEPDC5-Related Familial Focal Epilepsy: Case Series and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Xuan Zhang ◽  
Zhaoyang Huang ◽  
Jianghong Liu ◽  
Mingyu Li ◽  
Xiaoling Zhao ◽  
...  
Keyword(s):  
Frameshift Mutation ◽  
Focal Epilepsy ◽  
Clinical Manifestations ◽  
Case Series ◽  
Incomplete Penetrance ◽  
Splicing Mutation ◽  
Missense Mutations ◽  
Common Cause ◽  
Generation Sequencing

Mutations in the disheveled, Egl-10 and domain-containing protein 5 (DEPDC5) recently have been identified as a common cause of focal epilepsy syndromes. The association between phenotype and genotype of DEPDC5 mutation has not been adequately characterized. We studied four families with familial focal epilepsy carrying DEPDC5 mutations. Four novel DEPDC5 mutations were identified by next-generation sequencing, including two missense mutations (c.1729 >A and c.3260G>A), one splicing mutation (c.280-1G>A), and one frameshift mutation (c.515_516delinsT). We found that patients carrying different DEPDC5 mutation have different clinical manifestations. Incomplete penetrance is a prominent feature of DEPDC5-related epilepsy, with the rate of penetrance ranging from 25 to 100%. About 21.4% of patients with DEPDC5-related familial focal epilepsy are refractory to treatments. We further reviewed the correlation of genotype and phenotype in all previous literature regarding DEPDC5-related epilepsy. Our study suggested that the type of DEPDC5 mutation might provide important information for the prognosis evaluation.

scholarly journals Phenotypic and Genotypic Characterization of NPRL2-Related Epilepsy: Two Case Reports and Literature Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Yulin Sun ◽  
Lin Wan ◽  
Huimin Yan ◽  
Zhichao Li ◽  
Guang Yang
Keyword(s):  
Literature Review ◽  
Frameshift Mutation ◽  
Focal Epilepsy ◽  
Case Reports ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Pathogenic Variants ◽  
Treatment Processes ◽  
Generation Sequencing

The phenotype of nitrogen permease regulator-like 2 (NPRL2) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and infantile spasms (IS). The association between phenotype and genotype of NPRL2 variants has not been widely explored. This study aimed to explore the phenotype and genotype spectrum of NPRL2-related epilepsy. Here, we presented two clinical cases with NPRL2-related epilepsy, and discussed the characteristics, diagnosis, and treatment processes in the context of existing literature. Two novel NPRL2 likely pathogenic variants were identified by next-generation sequencing, including one splicing mutation (c.933-1G>A), and one frameshift mutation (c.257delG). The results of literature review showed that there were a total of 20 patients with NPRL2-related epilepsy whose mutations were mostly missense and hereditary. These findings indicate that the possibility of NPRL2 gene mutations in focal epilepsy should be considered for patients with family history, and that patients carrying different NPRL2 variants have different clinical manifestations. Our study expanded the genotype spectrum of NPRL2 and suggested that the type of NPRL2 variants might provide important information for the prognosis evaluation.

scholarly journals Heterogeneous clinical features in Cockayne syndrome-A patients with the same mutation and in siblings

2021 ◽  
Author(s):  
Asma CHIKHAOUI ◽  
Ichraf Kraoua ◽  
Nadège Calmels ◽  
Sami Bouchoucha ◽  
Cathy Obringer ◽  
...  
Keyword(s):  
North Africa ◽  
Clinical Symptoms ◽  
Excision Repair ◽  
Functional Characterization ◽  
Clinical Manifestations ◽  
Case Series ◽  
Cockayne Syndrome ◽  
The Other ◽  
Indel Mutation

Abstract Background Cockayne syndrome (CS) is a rare autosomal recessive disorder caused by mutations in ERCC6/CSB or ERCC8/CSA that participate in transcription-coupled nucleotide excision repair (TC-NER) of UV-induced DNA damage. CS patients display a large heterogeneity of clinical symptoms and severities, the reason of which is not fully understood, and little data is available for affected siblings. CS is largely undiagnosed in North Africa. Methods We report here the clinical description as well as genetic and functional characterization of eight North African CS patients, including siblings. These patients, who belonged to six unrelated families, underwent complete clinical examination and biochemical analyses. Sanger sequencing was performed for the recurrent mutation in five families, and targeted gene sequencing for one patient of the other family. We also performed RRS (Recovery RNA Synthesis) to confirm the functional impairment of DNA repair in the identified mutations. Results Six out of eight patients carried a homozygous indel mutation (c.598_600delinsAA) in exon 7 of ERCC8, and displayed a variable clinical spectrum, including between siblings, despite sharing the same mutation. The other two patients were Tunisian siblings who carried a homozygous splice-site variant in ERCC8 (c.843 + 1 G > C). They presented more severe clinical manifestations, which are in general rarely associated with CSA mutations, leading to gastrostomy and hepatic damage. Impaired TC-NER was confirmed by RRS in six tested patients. Conclusions This study provides the first deep characterization of case series of rare CS-A patients in North Africa. They carry mutations described to date only in this region and the Middle-East. We also provide the largest characterization of unrelated patients, as well as siblings, with the same mutation, providing a framework for dissecting elusive genotype-phenotype correlations in CS.

scholarly journals Characterization of a case series of Mastocytosis in a health care center in Cali, Colombia

2021 ◽  
Author(s):  
Daniela Marulanda Sandoval ◽  
Oscar Felipe Borja Montes ◽  
Jose Leonel Zambrano Urbano ◽  
Rigoberto Gomez Gutierrez
Keyword(s):  
World Literature ◽  
Case Reports ◽  
Care Center ◽  
Clinical Manifestations ◽  
Case Series ◽  
Poor Response ◽  
Skin Lesions ◽  
Serum Tryptase ◽  
Health Care Center

Abstract Mastocytosis is a group of rare diseases, which correspond to neoplasms of the myeloid lineage. In Colombia there are only case reports and so far there are no studies of greater extension. We conducted a case series in which an active search was made for patients with a diagnosis of mastocytosis, either cutaneous (CM) or systemic (SM), from the total number of consultations between June 2004 and June 2019 in the reference hemato-oncologic center ("mastocytosis"). A total of 4 cases of CM and 3 cases of SM were identified. The most frequent clinical manifestations were skin lesions, which were present in 100% of patients; of these hyperpigmented macules were the most frequent findings. Serum tryptase (TS) levels were found to be elevated in 67% (2/3) of patients with DM. Both TS levels and mean absolute eosinophils were higher in patients with MS. In this case series we found a higher frequency of extracutaneous involvement, and in general a very poor response to the management. The findings of this series are comparable to those reported in world literature.

scholarly journals Prevalence of the Brazilian TP53 Founder c.1010G>A (p.Arg337His) in Lung Adenocarcinoma: Is Genotyping Warranted in All Brazilian Patients?

2021 ◽  
Vol 12 ◽  
Author(s):  
Igor Araujo Vieira ◽  
Tiago Finger Andreis ◽  
Bruna Vieira Fernandes ◽  
Maria Isabel Achatz ◽  
Gabriel S. Macedo ◽  
...  
Keyword(s):  
General Population ◽  
Lung Adenocarcinoma ◽  
Case Series ◽  
Southeastern Brazil ◽  
Incomplete Penetrance ◽  
Genotype Frequencies ◽  
Central Regions ◽  
Variant Frequency ◽  
Tumor Dna ◽  
Generation Sequencing

In Southern and Southeastern Brazil, there is a germline pathogenic variant with incomplete penetrance located in the oligomerization domain of TP53, c.1010G>A (p.Arg337His). Due to a founder effect, the variant is present in 0.3% of the general population of the region. Recently, this variant was identified in 4.4 and 8.9% of two apparently unselected, single center case series of Brazilian lung adenocarcinoma (LUAD) patients from the Southeastern and Central regions of the country, respectively. In the present study, our aim was to examine TP53 c.1010G>A allele and genotype frequencies in LUAD samples obtained from patients diagnosed in Southern Brazil. A total of 586 LUAD samples (tumor DNA) recruited from multiple centers in the region were tested, and the mutant allele was identified using TaqMan® assays in seven cases (7/586, 1.2%) which were submitted to next generation sequencing analyses for confirmation. Somatic EGFR mutations were more frequent in TP53 c.1010G>A carriers than in non-carriers (57.1 vs. 17.6%, respectively). Further studies are needed to confirm if TP53 c.1010G>A is a driver in LUAD carcinogenesis and to verify if there is a combined effect of EGFR and germline TP53 c.1010G>A. Although variant frequency was higher than observed in the general population, it is less than previously reported in LUAD patients from other Brazilian regions. Additional data, producing regional allele frequency information in larger series of patients and including cost-effectiveness analyses, are necessary to determine if TP53 c.1010G>A screening in all Brazilian LUAD patients is justified.

scholarly journals Demographic and Clinical Features of Left Atrial Tumors in South Indian Population: A Case Series

2019 ◽  
pp. 1-6
Author(s):  
H.S Natraj Setty ◽  
Raghavendra Murthy P. ◽  
Krishnamurthy B.N ◽  
Shivanand S Patil ◽  
Veeresh Patil ◽  
...  
Keyword(s):  
Left Atrial ◽  
Indian Population ◽  
Clinical Manifestations ◽  
Case Series ◽  
Anatomical Location ◽  
South Indian Population ◽  
Primary Cardiac Tumor ◽  
South Indian ◽  
Atrial Tumors

Myxomas are the most common type of primary cardiac tumor. They cause a variety of clinical manifestations depending on size and anatomical location. Sometimes, manifestations are atypical challenging differential diagnosis and the therapeutic approach. Left atrial myxomas are commonly missed clinically and often lead to grave consequences. We present here a series of 6 cases of left atrial myxomas with demographic and clinical characterization of the patients that were managed successfully.

scholarly journals Case Report: Hereditary Alpha Tryptasemia in Children: A Pediatric Case Series and a Brief Overview of Literature

2021 ◽  
Vol 9 ◽  
Author(s):  
Daniele Zama ◽  
Edoardo Muratore ◽  
Arianna Giannetti ◽  
Iria Neri ◽  
Francesca Conti ◽  
...  
Keyword(s):  
Mast Cell ◽  
Differential Diagnosis ◽  
Cell Activation ◽  
Systemic Mastocytosis ◽  
Tertiary Care ◽  
Clinical Manifestations ◽  
Case Series ◽  
Mast Cell Activation ◽  
Genetic Trait

Hereditary alpha tryptasemia (HαT) is a recently described autosomal dominant genetic trait caused by an increased copy number of the TPSAB1 gene. It commonly leads to elevated basal serum tryptase levels, and it is associated with heterogeneous clinical manifestations. Some individuals report few to no symptoms, while others present with a spectrum of debilitating features. Most symptoms related to HαT may be explained by mast cell activation and mediator release, namely multiple allergies, anaphylaxis, and skin rash. However, the genotype-phenotype correlation has not yet been clearly understood. In particular, the characterization of the clinical spectrum lacks in children, where differential diagnosis could be challenging. Systemic mastocytosis, HαT, and mast cell activation syndrome are all associated with overlapping pathophysiology and symptoms, making the distinction between these conditions a difficult task. We herein describe two pediatric cases of HαT and their respective families at our tertiary care teaching hospital, highlighting the diagnostic workup and differential diagnosis. We also provide a brief review of the literature to underline the peculiar features of this condition in children.

scholarly journals Clinical and tomographic characterization of patients with interstitial lung disease at the Trujillo Regional Teaching Hospital, Peru

Medwave ◽  
2021 ◽  
Vol 21 (05) ◽  
pp. e8221-e8221
Author(s):  
Luis Alejandro Rodríguez-Hidalgo ◽  
Luis Alberto Concepción-Urteaga ◽  
Julio Santos Hilario-Vargas ◽  
Jorge Luis Cornejo-Portella ◽  
Oscar Nieri Alquizar-Horna
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Interstitial Pneumonia ◽  
Teaching Hospital ◽  
Usual Interstitial Pneumonia ◽  
Connective Tissue Diseases ◽  
Clinical Manifestations ◽  
Case Series ◽  
Interstitial Pulmonary Disease

Objective To determine the main clinical and tomographic characteristics of patients with diffuse interstitial lung disease at Trujillo Regional Teaching Hospital. Methods Case series. Tomographic examinations and clinical data were obtained from patients with interstitial pulmonary disease who attended the pulmonology service of Trujillo Regional Teaching Hospital. The information collected was recorded and systematized in Excel. For the statistical analysis, SPSS 23.0 program was used. Results Data from 103 patients were obtained, of which 60.2% were female, and 39.8% were male. The average age was 72 years for both groups. Main clinical manifestations were cough (82.5%), dyspnea (76.7%), joint pain (43.7%), weight loss (40.8%), velcro crackles (35%) and digital clubbing (28.2%). Exposure to wood smoke was present in 46.6%, exposure to inorganic dust in 12.6% and fowl ownership in 9.7% of cases. Thirty-one (30.1%) patients presented comorbidities. Among these, rheumatic diseases and arterial hypertension were the most frequent. Non-specific interstitial pneumonia pattern was present in 26.2% of the cases; probable usual interstitial pneumonia in 16.5%; organized type in 12.6%; usual interstitial in 10.7%; acute interstitial in 2.9% and 27.1% had no defined tomographic pattern. Conclusions In the studied population, clinical and tomographic characteristics of interstitial lung parenchymal diseases are variable in magnitude and forms of presentation. Female sex and exposure to fuels were the most frequent associated factors. Connective tissue diseases could also explain study findings.

scholarly journals Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients With RAG1/2 Mutations: First Cases Series From Mexico and Description of Two Novel Mutations.

2021 ◽  
Author(s):  
Mario Ernesto Cruz-Munoz ◽  
Saul Oswaldo Lugo-Reyes ◽  
Nina Pastor ◽  
Edith González-Serrano ◽  
Marco Yamazaki-Nakashimada ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Severe Combined Immunodeficiency ◽  
Clinical Manifestations ◽  
Case Series ◽  
Missense Mutations ◽  
Antigen Receptors ◽  
Novel Mutations ◽  
Nonsense Mutations ◽  
First Case ◽  
Immunological Phenotype

Abstract Mutations in Recombinase Activating Genes 1 and 2 (RAG1/2) results in human severe combined immunodeficiency (SCID). The products of these genes, are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Nonsense mutations in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with missense mutations may develop leaky SCID or Omenn syndrome (OS). A group of non-previously recognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two previously unidentified variants as causative of pathological manifestations associated to immunodeficiency. This study represents the first case series of RAG1 or RAG2 deficient patients from Mexico and Latin America.

scholarly journals Characterization of SARS-CoV-2 different variants and related morbidity and mortality: a systematic review

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
SeyedAhmad SeyedAlinaghi ◽  
Pegah Mirzapour ◽  
Omid Dadras ◽  
Zahra Pashaei ◽  
Amirali Karimi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Manifestations ◽  
Morbidity And Mortality ◽  
Current Evidence ◽  
N Gene ◽  
Missense Mutations ◽  
Global Pandemic ◽  
Online Databases ◽  
Life Threatening

Abstract Introduction Coronavirus Disease-2019 (SARS-CoV-2) started its devastating trajectory into a global pandemic in Wuhan, China, in December 2019. Ever since, several variants of SARS-CoV-2 have been identified. In the present review, we aimed to characterize the different variants of SARS-CoV-2 and explore the related morbidity and mortality. Methods A systematic review including the current evidence related to different variants of SARS-CoV-2 and the related morbidity and mortality was conducted through a systematic search utilizing the keywords in the online databases including Scopus, PubMed, Web of Science, and Science Direct; we retrieved all related papers and reports published in English from December 2019 to September 2020. Results A review of identified articles has shown three main genomic variants, including type A, type B, and type C. we also identified three clades including S, V, and G. Studies have demonstrated that the C14408T and A23403G alterations in the Nsp12 and S proteins are the most prominent alterations in the world, leading to life-threatening mutations.The spike D614G amino acid change has become the most common variant since December 2019. From missense mutations found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in the nucleocapsid (N) gene was significantly associated with patients' mortality. The other significant deleterious variant (G25563T) is found in patients located in Orf3a and has a potential role in viral pathogenesis. Conclusion Overall, researchers identified several SARS-CoV-2 variants changing clinical manifestations and increasing the transmissibility, morbidity, and mortality of COVID-19. This should be considered in current practice and interventions to combat the pandemic and prevent related morbidity and mortality.

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