scholarly journals Novel In-Frame Deletion in HTRA1 Gene, Responsible for Stroke at a Young Age and Dementia—A Case Study

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1955
Author(s):  
Julija Grigaitė ◽  
Kamilė Šiaurytė ◽  
Eglė Audronytė ◽  
Eglė Preikšaitienė ◽  
Birutė Burnytė ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Brain Magnetic Resonance Imaging ◽  
In Silico Analysis ◽  
Magnetic Resonance Imaging Mri ◽  
Biallelic Mutations ◽  
Population Databases ◽  
Autosomal Recessive Manner ◽  
Cerebral Small Vessel Diseases

Biallelic mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene are known to cause an extremely rare cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which belongs to the group of hereditary cerebral small vessel diseases and is mainly observed in the Japanese population. Even though this pathology is inherited in an autosomal recessive manner, recent studies have described symptomatic carriers with heterozygous HTRA1 mutations who have milder symptoms than patients with biallelic HTRA1 mutations. We present the case of a Lithuanian male patient who had a stroke at the age of 36, experienced several transient ischemic attacks, and developed an early onset, progressing dementia. These clinical symptoms were associated with extensive leukoencephalopathy, lacunar infarcts, and microbleeds based on brain magnetic resonance imaging (MRI). A novel heterozygous in-frame HTRA1 gene deletion (NM_002775.5:c.533_535del; NP_002766.1:p.(Lys178del)) was identified by next generation sequencing. The variant was consistent with the patient’s phenotype, which could not be explained by alternative causes, appeared highly deleterious after in silico analysis, and was not reported in the medical literature or population databases to date.

Epilepsy in Propionic Acidemia: Case Series of 14 Saudi Patients

2018 ◽  
Vol 33 (11) ◽  
pp. 713-717 ◽  
Author(s):  
Afnan AlGhamdi ◽  
Muhammad Talal Alrifai ◽  
Abdullah I. Al Hammad ◽  
Fuad Al Mutairi ◽  
Abdulrahman Alswaid ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Case Series ◽  
Brain Magnetic Resonance Imaging ◽  
Propionic Acidemia ◽  
Resonance Imaging ◽  
Mri Findings ◽  
Epileptiform Discharges ◽  
Magnetic Resonance Imaging Mri ◽  
Autosomal Recessive Manner ◽  
Delayed Myelination

Propionic acidemia is an inborn error of metabolism that is inherited in an autosomal recessive manner. It is characterized by a deficient propionyl-CoA carboxylase due to mutations in either of its beta or alpha subunits. In the literature, there is a clear association between propionic acidemia and epilepsy. In this cohort, we retrospectively reviewed the data of 14 propionic acidemia patients in Saudi Arabia and compared the findings to those of former studies. Six of the 14 (43%) patients developed epileptic seizure, mainly focal seizures. All patients were responsive to conventional antiepileptic drugs as their seizures are controlled. The predominant electroencephalographic (EEG) findings were diffuse slowing in 43% and multifocal epileptiform discharges in 14% of the patients. In 1 patient, burst suppression pattern was detected, a pattern never before reported in patients with propionic acidemia. Brain magnetic resonance imaging (MRI) findings mainly consisted of signal changes of the basal ganglia (36%), generalized brain atrophy (43%), and delayed myelination (43%).The most common genotype in our series is the homozygous missense mutation in the PCCA gene (c.425G>A; p. Gly142Asp). However, there is no clear genotype–seizure correlation. We conclude that seizure is not an uncommon finding in patients with propionic acidemia and not difficult to control. Additional studies are needed to further elaborate on genotype–seizure correlation.

scholarly journals Biallelic SCN2A Gene Mutation Causing Early Infantile Epileptic Encephalopathy: Case Report and Review

2019 ◽  
Vol 11 ◽  
pp. 117957351984993 ◽  
Author(s):  
Shahad AlSaif ◽  
Muhammad Umair ◽  
Majid Alfadhel
Keyword(s):  
Autosomal Recessive ◽  
Brain Magnetic Resonance Imaging ◽  
Autosomal Recessive Inheritance ◽  
Epileptic Encephalopathy ◽  
Normal Brain ◽  
Infantile Seizures ◽  
Gene Defects ◽  
Magnetic Resonance Imaging Mri ◽  
Neuronal Type

The voltage-gated sodium channel neuronal type 2 alpha subunit (Navα1.2) encoded by the SCN2A gene causes early infantile epileptic encephalopathy (EIEE) inherited in an autosomal dominant manner. Clinically, it has variable presentations, ranging from benign familial infantile seizures (BFIS) to severe EIEE. Diagnosis is achieved through molecular DNA testing of the SCN2A gene. Herein, we report on a 30-month-old Saudi girl who presented on the fourth day of life with EIEE, normal brain magnetic resonance imaging (MRI), normal electroencephalography (EEG), and well-controlled seizures. Genetic investigation revealed a novel homozygous missense mutation (c.5242A > G; p.Asn1748Asp) in the SCN2A gene (NM_001040142.1). This is the first reported autosomal recessive inheritance of a disease allele in the SCN2A and therefore expands the molecular and inheritance spectrum of the SCN2A gene defects.

scholarly journals Mutation in the RPE65 gene causing hereditary retinal dystrophy in the Briard dogs: application of a new detection method

2008 ◽  
Vol 53 (No. 4) ◽  
pp. 176-179
Author(s):  
R. Bechyňová ◽  
J. Dostál ◽  
A. Stratil ◽  
F. Jílek ◽  
P. Horák
Keyword(s):  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Stop Codon ◽  
Retinal Dystrophy ◽  
Premature Stop Codon ◽  
Causative Mutation ◽  
Functional Protein ◽  
Hereditary Retinal Dystrophy ◽  
Briard Dogs ◽  
Autosomal Recessive Manner

Inherited eye diseases are widespread in most of the pure dog breeds and they show a severe impact on canine health, welfare and working ability. Congenital stationary night blindness (CSNB) was originally described in Briards. CSNB is slow progressive retinal degeneration with very early onset of clinical symptoms and is inherited in an autosomal recessive manner. The causative mutation (Y16567.1:c.487_490delAAGA) for CSNB was identified in exon 5 of the <I>RPE6</I>5 gene. This deletion results in a frameshift and leads to a premature stop codon and expression of a non-functional protein. To date, only expensive, laborious or unpractical methods have been used for detection of the mutation in the canine <I>RPE65</I> gene. The main goals of this study were to develop a new method for routine genotyping of the causative mutation and to assess its occurrence in the Czech population of Briards. The method of electrophoresis in the gel Spraedex EL600 can be widely used for genotyping of the <I>RPE65</I> gene as a basis of proper genetic counselling and an improvement of genetic health in the Briard populations. In the studied population, the following frequencies of alleles + (wild) and – (mutant) were observed – 0.939 and 0.061, respectively.

scholarly journals C4OH is a Potential Screening Marker - A Multicenter Retrospective Study of Patients with Beta-Ketothiolase Deficiency in China

2020 ◽  
Author(s):  
Yiming Lin ◽  
Zhantao Yang ◽  
Chiju Yang ◽  
Haili Hu ◽  
Haiyan He ◽  
...  
Keyword(s):  
Chinese Population ◽  
Autosomal Recessive ◽  
Clinical Symptoms ◽  
Autosomal Recessive Disorder ◽  
Urinary Organic Acid ◽  
Mutational Spectrum ◽  
Molecular Profiles ◽  
Biallelic Mutations ◽  
Almost All ◽  
Screening Marker

Abstract Background: Beta-ketothiolase deficiency (BKTD) is an autosomal recessive disorder caused by biallelic mutations in ACAT1 that affects both isoleucine catabolism and ketolysis. Scant information is available regarding the incidence, newborn screening (NBS), and mutational spectrum in China.Methods: We collected NBS, biochemical, clinical, and ACAT1 mutation data from 18 provinces or municipalities in China between January 2009 and May 2020, and systematically assessed all available published Chinese BKTD patients data.Results: Totally 16,088,190 newborns were screened and 14 were identified through NBS, with an estimated incidence of 1 per 1 million newborns in China. Twenty-nine patients were genetically diagnosed as BKTD and 12 patients were newly identified. Most patients showed typical blood acylcarnitine and urinary organic acid profiles. In particular, almost all patients (15/16, 94%) showed elevated C4OH levels. Eighteen patients presented acute metabolic decompensations and displayed variable clinical symptoms. The acute episodes of 9 patients were triggered by infections, diarrhea, and vaccination. About two thirds of patients have favorable outcomes, one showed developmental delay, while three had died. Twenty-seven distinct variants were identified in ACAT1, among which 5 were found to be novel.Conclusion: This study presented the largest series of BKTD cohort in China. Our results indicated that C4OH is a useful marker for the detection of BKTD. The performance of BKTD NBS could be improved by adding C4OH to the current panel of C5OH and C5:1 markers in NBS. The mutational spectrum and molecular profiles of ACAT1 in Chinese population were expanded with 5 newly identified variants.

scholarly journals Case Report: Prominent Brainstem Involvement in Two Patients With Anti-CASPR2 Antibody-Associated Autoimmune Encephalitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Pei Liu ◽  
Miao Bai ◽  
Chao Ma ◽  
Yaping Yan ◽  
Gejuan Zhang ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Clinical Symptoms ◽  
Brain Magnetic Resonance Imaging ◽  
Autoimmune Encephalitis ◽  
Cerebellar Hemisphere ◽  
Gradual Improvement ◽  
Brainstem Lesions ◽  
First Case ◽  
Magnetic Resonance Imaging Mri ◽  
Igg1 Subclass

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

A controlled Valsalva Maneuver causes neither Diffusion-Positive Hippocampal Lesions nor Clinical Symptoms after Transient Global Amnesia

2019 ◽  
Vol 82 (4-6) ◽  
pp. 113-115
Author(s):  
Manuel Gomez-Choco ◽  
Ariel Fernando Mariaca ◽  
Christian Gaebel ◽  
José Manuel Valdueza
Keyword(s):  
Clinical Symptoms ◽  
Valsalva Maneuver ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Transient Global Amnesia ◽  
Resonance Imaging ◽  
Hippocampal Lesions ◽  
Global Amnesia ◽  
Magnetic Resonance Imaging Mri ◽  
Age Range

Valsalva maneuver (VM) precedes frequently transient global amnesia (TGA) and up to 84% of the patients with TGA present hippocampal diffusion-weighted imaging-positive (DWI+) lesions on brain magnetic resonance imaging (MRI). We studied 20 patients with TGA and hippocampal DWI+ lesions. Median age (range) of the patients was 67 (57–80) years and 55% were women. TGA had been preceded by a VM-associated activity in 14 patients (70%), and brain MRI had been performed at a median (range) of 47.5 (42–79) h after TGA. These patients underwent a second MRI after a controlled-induced VM at least 3 months after TGA. This MRI was performed at a median (range) of 46.8 (41–138) h after the controlled-induced VM. None of the patients who reproduced TGA symptoms presented new DWI+ lesions on the second MRI. In patients with a previous episode of TGA, VM cannot elicit TGA in isolation and the interplay of other simultaneous factors is needed.

Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families

2021 ◽  
pp. bjophthalmol-2020-318204
Author(s):  
Zohra Chibani ◽  
Imen Zone Abid ◽  
Peter Söderkvist ◽  
Jamel Feki ◽  
Mounira Hmani Aifa
Keyword(s):  
Autosomal Recessive ◽  
Corneal Transplantation ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Corneal Dystrophy ◽  
Solute Carrier Family ◽  
Transporter Protein ◽  
Bicarbonate Transporter ◽  
Corneal Clouding ◽  
Solute Carrier

BackgroundAutosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).MethodsTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.ResultsA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.ConclusionTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.

scholarly journals Identifying a Common Functional Framework for Apathy Large-Scale Brain Network

2021 ◽  
Vol 11 (7) ◽  
pp. 679
Author(s):  
Vincenzo Alfano ◽  
Mariachiara Longarzo ◽  
Giulia Mele ◽  
Marcello Esposito ◽  
Marco Aiello ◽  
...  
Keyword(s):  
Large Scale ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Network ◽  
Neural Pathways ◽  
Resonance Imaging ◽  
Daily Life Activities ◽  
Functional Differences ◽  
Central Gyrus ◽  
Magnetic Resonance Imaging Mri ◽  
Disease Specific

Apathy is a neuropsychiatric condition characterized by reduced motivation, initiative, and interest in daily life activities, and it is commonly reported in several neurodegenerative disorders. The study aims to investigate large-scale brain networks involved in apathy syndrome in patients with frontotemporal dementia (FTD) and Parkinson’s disease (PD) compared to a group of healthy controls (HC). The study sample includes a total of 60 subjects: 20 apathetic FTD and PD patients, 20 non apathetic FTD and PD patients, and 20 HC matched for age. Two disease-specific apathy-evaluation scales were used to measure the presence of apathy in FTD and PD patients; in the same day, a 3T brain magnetic resonance imaging (MRI) with structural and resting-state functional (fMRI) sequences was acquired. Differences in functional connectivity (FC) were assessed between apathetic and non-apathetic patients with and without primary clinical diagnosis revealed, using a whole-brain, seed-to-seed approach. A significant hypoconnectivity between apathetic patients (both FTD and PD) and HC was detected between left planum polare and both right pre- or post-central gyrus. Finally, to investigate whether such neural alterations were due to the underlying neurodegenerative pathology, we replicated the analysis by considering two independent patients’ samples (i.e., non-apathetic PD and FTD). In these groups, functional differences were no longer detected. These alterations may subtend the involvement of neural pathways implicated in a specific reduction of information/elaboration processing and motor outcome in apathetic patients.

Acute Strokelike Presentation and Long-term Evolution of Diffusion Restriction Pattern in Ethylmalonic Encephalopathy

2021 ◽  
pp. 088307382110065
Author(s):  
Jaehyung Lim ◽  
Brian J. Shayota ◽  
Erica Lay ◽  
Sarah H. Elsea ◽  
Mir Reza Bekheirnia ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Mitochondrial Disorder ◽  
Brain Magnetic Resonance Imaging ◽  
Restriction Pattern ◽  
Spastic Diplegia ◽  
Ethylmalonic Encephalopathy ◽  
Developmental Regression ◽  
Downstream Effects ◽  
Cystic Changes

Ethylmalonic encephalopathy is a rare autosomal recessive mitochondrial disorder caused by pathogenic biallelic variants in the ETHE1 gene. The phenotype of this disease has been attributed to deficiency in the mitochondrial sulfur dioxygenase leading to many downstream effects. Ethylmalonic encephalopathy classically presents with developmental regression, petechiae, acrocyanosis, and chronic diarrhea. The neurologic phenotype includes hypotonia, spastic diplegia, ataxia, and developmental delay. As more patients with this condition are described, the neurologic phenotype continues to expand. Although strokelike episodes or metabolic strokes have been studied in other mitochondrial disorders, they have not been thoroughly reported in this disorder. Herein, we describe 3 patients with ethylmalonic encephalopathy who presented clinically with strokelike episodes and strokelike abnormalities on brain magnetic resonance imaging in the setting of acute illness, and the long-term sequelae with evolution into cystic changes in one of these subjects.

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