scholarly journals A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Kao-Min Lin ◽  
Geng Su ◽  
Fengpeng Wang ◽  
Xiaobin Zhang ◽  
Yuanqing Wang ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Exome Sequencing ◽  
De Novo ◽  
Intractable Epilepsy ◽  
Bioinformatic Analysis ◽  
Epileptic Encephalopathy ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Targeted Exome Sequencing ◽  
Complex Disorder

Abstract Background Epilepsy is a complex disorder caused by various factors, including genetic aberrance. Recent studies have identified an essential role of the sodium channel Nav1.6, encoded by the gene SCN8A, in epileptic encephalopathy. Case presentation Using parent-offspring trio targeted-exome sequencing, we identified a de novo heterozygous missense mutation c.3953A > G (p.N1318S) in SCN8A in a 3-year-and-9-month Chinese female patient with early infantile epileptic encephalopathy and a normal magnetic resonance imaging of the brain. Conclusions This de novo mutation was only detected in the patient but not in her parents. Bioinformatic analysis indicates the pathogenicity of this mutation. Administration of the sodium channel blocker well controlled seizures in the patient. Therefore, we recommend trio targeted-exome sequencing as a routine method for pathogenic variant screening in patients with intractable epilepsy and a normal MRI.

Exome Sequencing Identifying Dual Mutations in Calcium Signaling Genes GNAO1 and ATP2B3 in a Patient with Early Infantile Epileptic Encephalopathy

2016 ◽  
Vol 15 (04) ◽  
pp. 183-186
Author(s):  
Fatema Serajee ◽  
Ahm Huq ◽  
Keisuke Ueda
Keyword(s):  
Calcium Signaling ◽  
Exome Sequencing ◽  
Missense Mutation ◽  
Calcium Homeostasis ◽  
De Novo ◽  
Intractable Epilepsy ◽  
Epileptic Encephalopathy ◽  
Protein Signaling ◽  
Whole Exome ◽  
Spinocerebellar Ataxia 1

Early infantile epileptic encephalopathy (EIEE) is an age-dependent epileptic encephalopathy. It occurs early in life with various types of seizures, especially tonic spasms and its overall prognosis is poor. We report a 5-year-old boy with EIEE, severe developmental delay, intractable epilepsy, and congenital cerebellar ataxia. His infantile spasms were treated successfully with ACTH, but he later developed intractable focal seizures. Whole exome sequencing revealed a maternally inherited missense mutation in the ATP2B3 gene (c.3338C > T/p.T1113M) and a de novo missense mutation in the GNAO1 gene (c.133G > C/p.G45R). Both genes are associated with calcium signaling pathways. The ATP2B3 gene is associated with intracellular calcium clearance, resulting in abnormal calcium homeostasis and X-linked spinocerebellar ataxia-1. The GNAO1 gene is associated with G protein signaling, affecting calcium signaling, and EIEE. Both mutations are related to maintain cellular calcium homeostasis, but the phenotype was not significantly more severe than those which have been reported.

scholarly journals Developmental encephalopathy and epilepsy associated with a heterozygous de novo mutation in the IRF2BPL gene: a case report

2021 ◽  
Vol 16 (1-2) ◽  
pp. 69-75
Author(s):  
N. G. Lyukshina ◽  
A. A. Sharkov ◽  
E. N. Tolmacheva
Keyword(s):  
De Novo ◽  
Cerebellar Atrophy ◽  
Epileptic Encephalopathy ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Normal Brain ◽  
Facial Phenotype ◽  
Clonic Seizures ◽  
De Novo Variant ◽  
Normal Brain Development

Developmental encephalopathy with epilepsy or epileptic encephalopathy, associated with a heterozygous mutation in the IRF2BPL gene, is a rare severe disorder. It’s manifested by developmental delay or regression of skills until or after epilepsy onset. Patients have a specific facial phenotype, movement disorders with dystonia and choreoathetosis, ataxia, dysarthria, dysmetria, and dysdiadochokinesis. Epilepsy is a common manifestation of the disease (around 70 % of cases), from the age of 6 months to 26 years. Semiology of seizures is vary, including infantile spasms, myoclonic, tonic or clonic seizures with nonspecific electroencephalographic changes. magnetic resonance imaging shows normal brain development at an early age and cortical and cerebellar atrophy developing over time. The authors present a clinical case describing a patient with a causative de novo variant (c.2152delT) in the IRF2BPL gene in Russia.This patient was included to common table in an article entitled “De novo truncating variants in the intronless IRF2BPL are responsible for developmental epileptic encephalopathy” (DOI: 10.1038/s41436-018-0143-0).

scholarly journals Early diagnosis of a newborn with tuberous sclerosis caused by a genetic mutation

2021 ◽  
Vol 49 (8) ◽  
pp. 030006052110358
Author(s):  
Lin Qiao ◽  
Yuting Yang ◽  
Dongmei Yue
Keyword(s):  
Genetic Testing ◽  
Early Diagnosis ◽  
Tuberous Sclerosis ◽  
De Novo ◽  
Clinical Manifestations ◽  
De Novo Mutation ◽  
Heterozygous Mutation ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Tsc1 Gene

Objective Tuberous sclerosis (TSC) is an autosomal dominant disorder, often detected during childhood. We present the results of genetic testing in a newborn with suspected TSC. Methods A newborn with no specific clinical manifestations of TSC showed evidence of TSC on magnetic resonance imaging and echocardiography. Next-generation sequencing (NGS) and multiple ligation-dependent probe amplification (MLPA) of the TSC1 and TSC2 gene exons were carried out to confirm the diagnosis. Results The results of MLPA were negative, but NGS showed a heterozygous mutation in the TSC1 gene comprising insertion of a T residue at c.2165 (exon 17) to c.2166 (exon 17), indicating a loss of function mutation. These results were verified by Sanger sequencing. This genetic change was present in the newborn but the parental genotypes were wild-type, indicating a de novo mutation. Conclusions In this case, a case of TSC caused by a heterozygous mutation in the TSC1 gene was confirmed by NGS sequencing. This indicates the suitability of genetic testing for the early diagnosis of clinically rare and difficult-to-diagnose diseases, to guide clinical treatment.

scholarly journals A de novo Mutation in the SCN4A Gene Causing Sodium Channel Myotonia

2015 ◽  
Vol 2 (2) ◽  
pp. 181-184 ◽  
Author(s):  
Kristin Ørstavik ◽  
Sean Ciaran Wallace ◽  
Torberg Torbergsen ◽  
Angela Abicht ◽  
Svein Erik Tangsrud ◽  
...  
Keyword(s):  
Sodium Channel ◽  
De Novo ◽  
De Novo Mutation

A case of early onset epileptic encephalopathy with de novo mutation in SLC35A2: Clinical features and treatment for epilepsy

2017 ◽  
Vol 39 (3) ◽  
pp. 256-260 ◽  
Author(s):  
Tomokazu Kimizu ◽  
Yukitoshi Takahashi ◽  
Taikan Oboshi ◽  
Asako Horino ◽  
Takayoshi Koike ◽  
...  
Keyword(s):  
Clinical Features ◽  
Early Onset ◽  
De Novo ◽  
Epileptic Encephalopathy ◽  
De Novo Mutation

scholarly journals A De Novo Mutation in the Sodium-Activated Potassium Channel KCNT2 Alters Ion Selectivity and Causes Epileptic Encephalopathy

Cell Reports ◽  
2017 ◽  
Vol 21 (4) ◽  
pp. 926-933 ◽  
Author(s):  
Sushmitha Gururaj ◽  
Elizabeth Emma Palmer ◽  
Garrett D. Sheehan ◽  
Tejaswi Kandula ◽  
Rebecca Macintosh ◽  
...  
Keyword(s):  
Potassium Channel ◽  
De Novo ◽  
Ion Selectivity ◽  
Epileptic Encephalopathy ◽  
De Novo Mutation

scholarly journals Identification of Novel ADGRV1 and KCNC2 Variants Using Whole-Exome Sequencing in Two Colombian Patients with Usher and Encephalopathy Syndromes

2021 ◽  
Author(s):  
Estephania Candelo ◽  
Lorena Diaz-Ordoñez ◽  
Rafael Pacheco ◽  
Emelina Ruiz ◽  
Harry Pachajoa
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Usher Syndrome ◽  
Epileptic Encephalopathy ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Epilepsy Syndrome ◽  
Compound Heterozygous ◽  
Whole Exome ◽  
Excellent Method

Abstract Introduction: Usher syndrome has a broad phenotypic and genotypic spectrum. Developmental and epileptic encephalopathy-52 (DEE52) is a sever autosomal recessive seizure disorder that is characterized by infantile onset of refractory seizures, consequently resulting in delayed global development. This study aimed to describe the clinical features and to investigate the four variants identified in a Colombian family with Usher syndrome and KCNC2 encephalopathy syndrome.Methods and Results: We present a case of a family with two clinically relevant phenotypes: a mother with a compound heterozygous mutation causing Usher Syndrome, type IIC (USH2C) and her 15-year-old son who carried one heterozygous variant in the KCNC2 gene (p.P470S) and two cis mutations (p.V2927I and p.Q4955EfsTer10) in the ADGRV1 gene segregated from his mother, and a second non-disrupted allele. Owing to this, the boy did not present with USH2C but presented a developmental epilepsy syndrome. His younger sibling was unaffected, although he did inherit the trans mutation in a single pathogenic allele from his mother.Discussion and Conclusion: Whole-exome sequencing helps detect genes related to known and novel hearing loss and seizure syndrome. However, familiar segregation studies are an excellent method to clarify genotype-phenotype correlation in families, where multiple genes of clinically relevant have been identified. This method helps determine the genotype-phenotype relationship of a disease, which is associated with the clinical presentation and determines the pathogenicity of variants that are classified as variants of uncertain clinical significance.

scholarly journals P.109 Diagnostic Yield of Targeted Exome Sequencing in West Syndrome

2021 ◽  
Vol 48 (s3) ◽  
pp. S50-S50
Author(s):  
M Parfyonov ◽  
I Guella ◽  
DM Evans ◽  
S Adam ◽  
C DeGuzman ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Genetic Heterogeneity ◽  
High Throughput Sequencing ◽  
De Novo ◽  
Diagnostic Yield ◽  
Genetic Diagnosis ◽  
West Syndrome ◽  
Global Developmental Delay ◽  
Targeted Exome Sequencing ◽  
Ion Proton

Background: West syndrome (WS) is characterized by the onset of epileptic spasms usually within the first year of life. Global developmental delay with/without regression is common. Advances in high-throughput sequencing have supported the genetic heterogeneity of this condition. To better understand the genetic causes of this disorder, we investigated the results of targeted exome sequencing in 29 patients with WS. Methods: Whole exome sequencing (WES) was performed on an Ion ProtonTM and variant reporting was restricted to sequences of 620 known epilepsy genes. Diagnostic yield and treatment impact are described for 29 patients with WS. Results: A definitely/likely diagnosis was made in 10 patients (34%), which included 10 different genes (ALG13, PAFAH1B1, SLC35A2, DYNC1H1, ADSL, DEPDC5, ARX, CDKL5, SCN8A, STXBP1) known to be associated with epilepsy or WS. Most variants were de novo dominant (X-linked/autosomal) except for ARX (X-linked recessive) and ADSL (autosomal recessive). 4 out of 10 (40%) had a genetic diagnosis with potential treatment implications. Conclusions: These results emphasize the genetic heterogeneity of WS. The high diagnostic yield, along with the significant genetic variability, and the potential for treatment impact, supports the early use of this testing in patients with unexplained WS.

scholarly journals Novel de novo heterozygous mutation on SYNGAP1 from the Indian population

2020 ◽  
Author(s):  
Vijaya Verma ◽  
Amit Mandora ◽  
Abhijeet Botre ◽  
James Premdoss Clement
Keyword(s):  
Exome Sequencing ◽  
De Novo ◽  
Novel Mutation ◽  
Autism Spectrum ◽  
Current Treatment ◽  
Developmental Trajectory ◽  
Global Developmental Delay ◽  
Heterozygous Mutation ◽  
Specific Gene ◽  
De Novo Mutations

Abstract Background : Exome sequencing is a prominent tool to identify novel and deleterious mutations which could be nonsense, frameshift, and canonical splice-site mutations in a specific gene. De novo mutations in SYNGAP1 , which codes for synaptic RAS-GTPase activating the protein, causes Intellectual disability (ID) and Autism Spectrum Disorder (ASD). SYNGAP1 related ASD/ID is one of the rare diseases that is detrimental to the normal neuronal developmental and disrupts the global development of a child. Results: We report a case of a child of 2-year old with global developmental delay, microcephaly subtle dysmorphism, absence seizures, disrupted sleep, delay in learning a language, and eating problems. Upon further validation, the child has a few traits of ASD. Here, based on focused exome sequencing, we report a de novo heterozygous mutation in SYNGAP1 exon 11 with c. 1861 C>T (p.arg612ter). Currently, the child is on atorvastatin and has shown considerable improvement in global behaviour and cognitive development. The long-term follow up of the child’s development would contribute to the already existing knowledge of the developmental trajectory in individuals with SYNGAP1 heterozygous mutation. Conclusion: In this report, we discuss the finding of a novel mutation in one of the genes, SYNGAP1 , implicated in ASD/ID. In addition, we discuss the current treatment prescribed to the patient and the progress of global developmental of the child.

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