scholarly journals Genetic epilepsy caused by CDKL5 gene mutations as an example of epileptic encephalopathy and developmental encephalopathy: literature review and own observations

2021 ◽  
Vol 16 (1-2) ◽  
pp. 10-41
Author(s):  
K. Yu. Mukhin ◽  
O. A. Pylaeva ◽  
M. Yu. Bobylova ◽  
V. A. Chadaev
Keyword(s):  
Literature Review ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Case Series ◽  
Gene Mutations ◽  
Epileptic Encephalopathy ◽  
Serine Threonine Kinase ◽  
Gene Encoding ◽  
Threonine Kinase

The disease caused by mutations in the CDKL5 gene (encoding cyclin-dependent kinase 5, CDK5) belongs to the group of early (infantile) epileptic encephalopathies caused by alterations in the genome. Currently, the disease is called “developmental encephalopathy and epileptic encephalopathy type 2”. This disorder is a complex combination of symptoms that develop due to deficiency or absence of the CDKL5 gene product, which is serine/threonine kinase. The CDKL5 gene is located on X chromosome; the disease has an X-linked dominant inheritance pattern. This literature review summarizes relevant studies analyzing the disease caused by CDKL5 gene mutations, including its genetic and epidemiological aspects, clinical manifestations, characteristics of epilepsy, principles of diagnosis, and therapeutic approaches. We present a case series of several patients with genetic disorders involving the CDKL5 gene.

scholarly journals Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

2020 ◽  
Vol 14 (3) ◽  
pp. 28-36
Author(s):  
E. L. Dadali ◽  
I. A. Akimova ◽  
F. A. Konovalov ◽  
P. A. Shatalov ◽  
A. Yu. Krasnenko ◽  
...  
Keyword(s):  
Genetic Variant ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Psychomotor Retardation ◽  
Dominant Inheritance ◽  
Common Genetic Variant ◽  
Genetic Characteristics

Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations. We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE. The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.

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 WNK4 Kinase: from structure to physiology

2021 ◽  
Author(s):  
Adrian Rafael Murillo-de-Ozores ◽  
Alejandro Rodriguez-Gama ◽  
Hector Carbajal-Contreras ◽  
Gerardo Gamba ◽  
Maria Castaneda-Bueno
Keyword(s):  
Oxidative Stress ◽  
Mouse Models ◽  
Serine Threonine Kinase ◽  
Gene Encoding ◽  
Threonine Kinase ◽  
Physiological Conditions ◽  
Different Levels ◽  
Familial Hyperkalemic Hypertension

With No Lysine (K) kinase 4 (WNK4) belongs to a serine-threonine kinase family characterized by the atypical positioning of its catalytic lysine. Despite the fact that WNK4 has been found in many tissues, the majority of its study has revolved around its function in the kidney, specifically as a positive regulator of the thiazide-sensitive NaCl cotransporter (NCC) in the distal convoluted tubule (DCT) of the nephron. This is explained by the description of gain-of-function mutations in the gene encoding WNK4 that cause Familial Hyperkalemic Hypertension (FHHt). This disease is mainly driven by increased downstream activation of the Ste20-related Proline Alanine Rich Kinase (SPAK)/Oxidative Stress Responsive Kinase 1 (OSR1)-NCC pathway, which increases salt reabsorption in the DCT and indirectly impairs renal K+ secretion. Here, we review the large volume of information that has accumulated about different aspects of WNK4 function. We first review the knowledge on WNK4 structure and enumerate the functional domains and motifs that have been characterized. Then, we discuss WNK4 physiological functions based on the information obtained from in vitro studies and from a diverse set of genetically modified mouse models with altered WNK4 function. We then review in vitro and in vivo evidence on the different levels of regulation of WNK4. Finally, we go through the evidence that has suggested how different physiological conditions act through WNK4 to modulate NCC activity.

scholarly journals Involvement of a Magnaporthe grisea Serine/Threonine Kinase Gene, MgATG1, in Appressorium Turgor and Pathogenesis

2007 ◽  
Vol 6 (6) ◽  
pp. 997-1005 ◽  
Author(s):  
Xiao-Hong Liu ◽  
Jian-Ping Lu ◽  
Lei Zhang ◽  
Bo Dong ◽  
Hang Min ◽  
...  
Keyword(s):  
Lipid Droplets ◽  
Magnaporthe Grisea ◽  
Normal Development ◽  
Normal Values ◽  
Turgor Pressure ◽  
Serine Threonine Kinase ◽  
Gene Encoding ◽  
Kinase Gene ◽  
Threonine Kinase ◽  
Delayed Initiation

ABSTRACT We isolated an MgATG1 gene encoding a serine/threonine protein kinase from the rice blast fungus Magnaporthe grisea. In the ΔMgatg1 mutant, in which the MgATG1 gene had been deleted, autophagy was blocked; the mutant also showed fewer lipid droplets in its conidia, lower turgor pressure of the appressorium, and such defects in morphogenesis as delayed initiation and slower germination of conidia. As a result of lower turgor pressure of the appressorium, the ΔMgatg1 mutant lost its ability to penetrate and infect the two host plants, namely, rice and barley. However, normal values of the parameters and infective abilities were restored on reintroducing an intact copy of the MgATG1 gene into the mutant. Autophagy is thus necessary for turnover of organic matter during the formation of conidia and appressoria and for normal development and pathogenicity in M. grisea.

scholarly journals pUL21 regulation of pUs3 Kinase Activity Influences the Nature of Nuclear Envelope Deformation by the HSV-2 Nuclear Egress Complex

2021 ◽  
Author(s):  
Jamil H Muradov ◽  
Renee L Finnen ◽  
Michael A Gulak ◽  
Thomas J. M. Hay ◽  
Bruce W Banfield
Keyword(s):  
Nuclear Envelope ◽  
Serine Threonine Kinase ◽  
Uniform Size ◽  
Threonine Kinase ◽  
Nuclear Egress ◽  
Sds Page ◽  
Infected Cells ◽  
Simplex Virus ◽  
In Cells

It is well established that the herpesvirus nuclear egress complex (NEC) has an intrinsic ability to deform membranes. During viral infection, the membrane-deformation activity of the NEC must be precisely regulated to ensure efficient nuclear egress of capsids. One viral protein known to regulate herpes simplex virus type 2 (HSV-2) NEC activity is the tegument protein pUL21. Cells infected with an HSV-2 mutant lacking pUL21 (ΔUL21) produced a slower migrating species of the viral serine/threonine kinase pUs3 that was shown to be a hyperphosphorylated form of the enzyme. Investigation of the pUs3 substrate profile in ΔUL21-infected cells revealed a prominent band with a molecular weight consistent with that of the NEC components pUL31 and pUL34. Phosphatase sensitivity and retarded mobility in phos-tag SDS-PAGE confirmed that both pUL31 and pUL34 were hyperphosphorylated by pUs3 in the absence of pUL21. To gain insight into the consequences of increased phosphorylation of NEC components, the architecture of the nuclear envelope in cells producing the HSV-2 NEC in the presence or absence of pUs3 was examined. In cells with robust NEC production, invaginations of the inner nuclear membrane were observed that contained budded vesicles of uniform size. By contrast, nuclear envelope deformations protruding outwards from the nucleus, were observed when pUs3 was included in transfections with the HSV-2 NEC. Finally, when pUL21 was included in transfections with the HSV-2 NEC and pUs3, decreased phosphorylation of NEC components was observed in comparison to transfections lacking pUL21. These results demonstrate that pUL21 influences the phosphorylation status of pUs3 and the HSV-2 NEC and that this has consequences for the architecture of the nuclear envelope.

scholarly journals Amelogenesis imperfecta: A case series

2021 ◽  
Vol 7 (3) ◽  
pp. 145-148
Author(s):  
Jijin M J ◽  
Thabsheera P P ◽  
Mohamed Labeeb K P ◽  
Anjana R
Keyword(s):  
Dental Treatment ◽  
Tooth Development ◽  
Genetic Disorders ◽  
Case Series ◽  
Gene Mutations ◽  
Amelogenesis Imperfecta ◽  
Clinical Case Study ◽  
Different Types

Amelogenesis imperfecta (AI) refers to a group of rare genetic disorders that involve tooth development and that are passed down through families as a dominant trait. This condition is characterized by abnormal enamel formation caused by gene mutations that alter the quality and/or quantity of enamel. This dental problem can impact both primary and permanent dentition, varies among affected individuals, and results in esthetic and functional problems. The treatment planning for patients with AI is related to many factors, including the age of the patient, the type and severity of the disorder, intraoral conditions, and the socioeconomic status of the patient. It is crucial to plan a proper remedy, which requires collaboration among dental specialties to execute comprehensive dental treatment in order to provide a long-term solution with adequate esthetics. This clinical case study looks at three different types of amelogenesis imperfecta patients.

scholarly journals Congenital Hepatic Fibrosis in Children and Adults: Clinical Manifestations, Management, and Outcome—Case Series and Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Beidi Zhu ◽  
Zunguo Du ◽  
Zhengxin Wang ◽  
Yang Li ◽  
Jiming Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Portal Hypertension ◽  
Literature Review ◽  
Hepatic Fibrosis ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Case Series ◽  
Congenital Hepatic Fibrosis ◽  
Multidisciplinary Cooperation ◽  
Central Nervous Systems

Background. Congenital hepatic fibrosis is a hereditary fibropolycystic disease caused by ductal plate malformation. It is characterized by portal hypertension, but the manifestations, management, and outcome vary in children and adults. To raise awareness of medical staff, we have comprehensively compared the clinical features of congenital hepatic fibrosis between children and adults. Methods. We retrospectively enrolled all patients diagnosed with congenital hepatic fibrosis at the Huashan Hospital from August 2015 to August 2017 and analyzed their familial, clinical, laboratory, imaging, treatment, and follow-up data in detail. In addition, we reviewed cases with congenital hepatic fibrosis reported in the past 20 years in China and analyzed them according to the patients’ age. Results. A total of eight patients were diagnosed with congenital hepatic fibrosis in the study, including four children and four adults. The onset age of the children, who suffered from severe complications of portal hypertension and needed liver transplantation, ranged from 1 to 15 years old. The disorder developed in adults aged 26 to 60 years old. Three adults complained of recurrent abnormal liver function at the onset of illness, and they mainly received conservative treatments. The literature review included 30 children and 33 adults. In comparison, hepatomegaly was more common in children than in adults (57% vs. 21%, p=0.004). Malformation of kidneys and bile duct abnormalities were common, and multisystem involvement included eyes, other digestive organs, and genital and central nervous systems. Conclusions. Serious complications of portal hypertension developed in children requiring liver transplantation, while adults often had mild-to-moderate liver injuries upon onset. Adults with CHF varied a lot in clinical manifestations. Multiorgan involvement and unusual course are helpful to make a diagnosis. Timely histological assessment by liver biopsy and multidisciplinary cooperation are crucial for definitive diagnosis and early intervention.

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