scholarly journals Pathogenic mutations in ARX, CDKL5 and STXBP1 genes are not associated with the early-onset epileptic encephalopathy in Malaysian pediatric patients: A pilot study

2018 ◽  
Vol 1 (3) ◽  
pp. 5-17
Author(s):  
Ameerah Jaafar ◽  
Feizel Alsiddiq ◽  
King Hwa Ling
Keyword(s):  
Early Onset ◽  
High Resolution Melting ◽  
Epileptic Encephalopathy ◽  
Cyclin Dependent Kinase ◽  
Conventional Pcr ◽  
Control Subjects ◽  
Pathogenic Mutations ◽  
Age Dependent ◽  
Melting Analysis ◽  
Preliminary Study

Gene mutation is one of the etiologies of early-onset epileptic encephalopathy (EOEE), an age-dependent seizure in infants, which leads to brain defects. Previous studies have shown that several genes namely, aristaless related homeobox (ARX), cyclin dependent kinase like 5 (CDKL5) and syntaxin binding protein 1 (STXBP1) are responsible for the pathophysiology of the syndrome. The study involved 20 EOEE patients and 60 control subjects, which aimed to investigate the clinical association of Malaysian EOEE subjects with 13 known pathogenic mutations in the genes of interest. In addition, the entire ARX exonic region was also sequenced for known and novel mutations. PCR specificity and efficiency were optimized using conventional PCR and High Resolution Melting Analysis (HRMA). All cases and approximately 10% of control amplicon samples were purified and subjected to DNA sequencing. All known mutations reported previously were not found in control subjects and Malaysian EOEE patients with 100% confirmation by sequencing results. Sequencing of ARX exonic regions of patient samples did not find any mutation in all exons. The preliminary study indicates that selected known pathogenic mutations of ARX, CDKL5 and STXBP1 are not associated with EOEE in Malaysian paediatric patients.

Cyclin-Dependent Kinase-Like 5 (CDKL5) Mutation Screening in Rett Syndrome and Related Disorders

2010 ◽  
Vol 13 (2) ◽  
pp. 168-178 ◽  
Author(s):  
Rose White ◽  
Gladys Ho ◽  
Swetlana Schmidt ◽  
Ingrid E. Scheffer ◽  
Alexandra Fischer ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Early Onset ◽  
De Novo ◽  
Wide Spectrum ◽  
Neurodevelopmental Disorder ◽  
Mutation Screening ◽  
Clinical Manifestations ◽  
Epileptic Encephalopathy ◽  
Cyclin Dependent Kinase ◽  
Aicardi Syndrome

AbstractRett syndrome (RTT) is a severe neurodevelopmental disorder affecting females almost exclusively and is characterized by a wide spectrum of clinical manifestations. Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene have been found in up to 95% of classical RTT cases and a lesser proportion of atypical cases. Recently, mutations in another X-linked gene, CDKL5 (cyclin-dependent kinase-like 5) have been found to cause atypical RTT, in particular the early onset seizure (Hanefeld variant) and one female with autism. In this study we screened several cohorts of children for CDKL5 mutations, totaling 316 patients, including individuals with a clinical diagnosis of RTT but who were negative for MECP2 mutations (n = 102), males with X-linked mental retardation (n = 9), patients with West syndrome (n = 52), patients with autism (n = 59), patients with epileptic encephalopathy (n = 33), patients with Aicardi syndrome (n = 7) and other patients with intellectual disability with or without seizures (n = 54). In all, seven polymorphic variations and four de novo mutations (c.586C>T [p.S196L]; c.58G>C [p.G20R]; c.2504delC [p.P835fs]; deletion of exons 1 - 3) were identified, and in all instances of the latter the clinical phenotype was that of an epileptic encephalopathy. These results suggest that pathogenic CDKL5 mutations are unlikely to be identified in the absence of severe early-onset seizures and highlight the importance of screening for large intragenic and whole gene deletions.

scholarly journals Association of early-onset epileptic encephalopathy with involuntary movements – Case series and literature review

2020 ◽  
pp. 100417
Author(s):  
Atsuko Arisaka ◽  
Mitsuko Nakashima ◽  
Satoko Kumada ◽  
Kenji Inoue ◽  
Hiroya Nishida ◽  
...  
Keyword(s):  
Literature Review ◽  
Early Onset ◽  
Case Series ◽  
Epileptic Encephalopathy ◽  
Involuntary Movements

scholarly journals Parental mosaicism in Marfan and Ehlers–Danlos syndromes and related disorders

2021 ◽  
Author(s):  
Bertrand Chesneau ◽  
Aurélie Plancke ◽  
Guillaume Rolland ◽  
Nicolas Chassaing ◽  
Christine Coubes ◽  
...  
Keyword(s):  
High Resolution ◽  
Marfan Syndrome ◽  
High Resolution Melting ◽  
De Novo ◽  
Direct Sequencing ◽  
Causal Variant ◽  
Connective Tissue Disorder ◽  
High Resolution Melting Analysis ◽  
Aortic Diseases ◽  
Melting Analysis

AbstractMarfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our “aortic diseases genes” NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient’s management.

scholarly journals Rapid detection of fungal pathogens in bronchoalveolar lavage samples using panfungal PCR combined with high resolution melting analysis

2016 ◽  
Vol 54 (7) ◽  
pp. 714-724 ◽  
Author(s):  
Matej Bezdicek ◽  
Martina Lengerova ◽  
Dita Ricna ◽  
Barbora Weinbergerova ◽  
Iva Kocmanova ◽  
...  
Keyword(s):  
High Resolution ◽  
Bronchoalveolar Lavage ◽  
Rapid Detection ◽  
Fungal Pathogens ◽  
High Resolution Melting ◽  
High Resolution Melting Analysis ◽  
Melting Analysis ◽  
Panfungal Pcr

High-resolution melting analysis for detection of MYH9 mutations

Platelets ◽  
2008 ◽  
Vol 19 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Dana Provaznikova ◽  
Tereza Kumstyrova ◽  
Roman Kotlin ◽  
Peter Salaj ◽  
Vaclav Matoska ◽  
...  
Keyword(s):  
High Resolution ◽  
High Resolution Melting ◽  
High Resolution Melting Analysis ◽  
Melting Analysis
Sign in / Sign up

Export Citation Format

Share Document