A Novel Mutation in Aicardi–Goutières' Syndrome: A Case Report

2020 ◽  
Author(s):  
Motahareh Sheikh-Hosseini ◽  
Mohammad Moarefzadeh ◽  
Hamideh Alavi-Moghaddam ◽  
Saeid Morovvati
Keyword(s):  
Neonatal Jaundice ◽  
Clinical Phenotype ◽  
Novel Mutation ◽  
Genetic Disorder ◽  
Cerebral Atrophy ◽  
Pathogenic Mutation ◽  
Consanguineous Marriage ◽  
The Other ◽  
Congenital Infections ◽  
History Of

AbstractAicardi–Goutières' syndrome (AGS) is a rare heterogeneous genetic disorder characterized by encephalopathy and may bear resemblance to congenital infections. The prevalence of AGS is estimated at more than 4,000 worldwide. Mutations in TREX1 gene are present in ∼22% of patients. We present the case of a 2-year-old boy who came to the Biogene laboratory (Tehran, Iran) with a constellation of congenital disorders but no clear diagnosis. His clinical phenotype consisted of neonatal jaundice, relative microcephaly with diffuse cerebral atrophy in both hemispheres, developmental delay, hypotonia, and nystagmus. There was history of parental consanguineous marriage and prematurity. In our study, a homozygous potentially pathogenic mutation in TREX1 gene associated with AGS1 was detected. This mutation has not been reported in the other patients with AGS. A novel frameshift homozygous potentially pathogenic mutation in TREX1 is postulated to be the cause of disease in our patient.

scholarly journals Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma

2015 ◽  
Vol 7 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Joao McONeil Plancher ◽  
Robert B. Hufnagel ◽  
Achala Vagal ◽  
Katrina Peariso ◽  
Howard M. Saal ◽  
...  
Keyword(s):  
Contrast Enhancement ◽  
Head Trauma ◽  
Small Vessel Disease ◽  
Genetic Disorder ◽  
Single Gene ◽  
Young Patients ◽  
Pathogenic Mutation ◽  
Small Vessel ◽  
Vessel Disease ◽  
History Of

With this case report, we would like to heighten the awareness of clinicians about COL4A1 as a single-gene disorder causing cerebral small vessel disease and describe a previously unreported pathogenic missense substitution in COL4A1 (p.Gly990Val) and a new clinical presentation. We identified a heterozygous putatively pathogenic mutation of COL4A1 in a 50-year-old female with a history of congenital cataracts and glaucoma who presented with multiple diffusion-positive infarcts and areas of contrast enhancement following mild head trauma. We believe that this presentation of multiple areas of acute brain and vascular injury in the setting of mild head trauma is a new manifestation of this genetic disorder. Imaging findings of multiple acute infarcts and regions of contrast enhancement with associated asymptomatic old deep microhemorrhages and leukomalacia in adults after head trauma should raise a high suspicion for a COL4A1 genetic disorder. Radiographic patterns of significant leukoaraiosis and deep microhemorrhages can also be seen in patients with long-standing vasculopathy associated with hypertension, which our patient lacked. Our findings demonstrate the utility of genetic screening for COL4A1 mutations in young patients who have small vessel vasculopathy on brain imaging but who do not have significant cardiovascular risk factors.

scholarly journals Alternating flexed-extended posturing in progressive supranuclear palsy

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Nobuyuki Ishii ◽  
Hitoshi Mochizuki
Keyword(s):  
Magnetic Resonance Imaging ◽  
Nursing Home ◽  
Magnetic Resonance ◽  
Progressive Supranuclear Palsy ◽  
Late Stage ◽  
Cerebral Atrophy ◽  
The Other ◽  
Resonance Imaging ◽  
History Of ◽  
The Brain

A 69-year-old man who had been bedridden in nursing home because of a 5-year history of progressive supranuclear palsy (PSP) was admitted due to aspiration pneumonia. Besides neck dystonia in extension, he showed “alternating flexed–extended posturing”, in which the arm was flexed on one side and extended on the other. Magnetic resonance imaging of the brain revealed global cerebral atrophy that predominantly affected the cortex and midbrain. The mechanisms of complex posturing in late-stage PSP may sometimes be related to decortication and decerebration as well as dystonia, and “alternating flexed–extended posturing” might be one of the phenotypes of pathological progression in PSP.

scholarly journals Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lazar Velicki ◽  
Djordje G. Jakovljevic ◽  
Andrej Preveden ◽  
Miodrag Golubovic ◽  
Marija Bjelobrk ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Clinical Phenotype ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Mitral Annulus ◽  
Genetic Determinants ◽  
Myosin Binding Protein ◽  
Number Of Patients ◽  
History Of ◽  
The Difference

Abstract Background Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations. Methods As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography. Results The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p = 0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p = 0.085). Laboratory analyses revealed normal levels of creatinine (85.5 ± 18.3 vs. 81.3 ± 16.4 µmol/l; p = 0.487) and blood urea nitrogen (10.2 ± 15.6 vs. 6.9 ± 3.9 mmol/l; p = 0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients carrying MYH7 mutation (33% vs. 10%; p = 0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p = 0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p = 0.001). The difference in diastolic function, i.e. E/e′ ratio between the two groups was also noted (MYBPC3 8.8 ± 3.3, MYH7 13.9 ± 6.9, p = 0.079). Conclusions Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

scholarly journals Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy 

2020 ◽  
Author(s):  
Lazar Velicki ◽  
Djordje G Jakovljevic ◽  
Andrej Preveden ◽  
Miodrag Golubovic ◽  
Marija Bjelobrk ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Clinical Phenotype ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Mitral Annulus ◽  
Genetic Determinants ◽  
Myosin Binding Protein ◽  
Number Of Patients ◽  
History Of ◽  
The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

scholarly journals Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy

2020 ◽  
Author(s):  
Lazar Velicki ◽  
Djordje G Jakovljevic ◽  
Andrej Preveden ◽  
Miodrag Golubovic ◽  
Marija Bjelobrk ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Clinical Phenotype ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Mitral Annulus ◽  
Genetic Determinants ◽  
Myosin Binding Protein ◽  
Number Of Patients ◽  
History Of ◽  
The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

2020 ◽  
Author(s):  
Haydar Bağış ◽  
Özden Öztürk ◽  
Semih Bolu ◽  
Bayram Taşkın
Keyword(s):  
Novel Mutation ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
The Other ◽  
Cornelia De Lange Syndrome ◽  
Other Hand ◽  
Wide Range ◽  
Cornelia De Lange

AbstractThe Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

scholarly journals Genetic Determinants of Clinical Phenotype in Hypertrophic Cardiomyopathy

2020 ◽  
Author(s):  
Lazar Velicki ◽  
Djordje G Jakovljevic ◽  
Andrej Preveden ◽  
Miodrag Golubovic ◽  
Marija Bjelobrk ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Clinical Phenotype ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Mitral Annulus ◽  
Genetic Determinants ◽  
Myosin Binding Protein ◽  
Number Of Patients ◽  
History Of ◽  
The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

scholarly journals Favorable response to carbamazepine therapy in genetically proven myoclonus-dystonia child

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Mohammed F. Aljabri ◽  
Naglaa M. Kamal ◽  
Abdulrhman Alghamdi ◽  
Hamdan Alghamdi ◽  
Naif Alomairi
Keyword(s):  
Genetic Disorder ◽  
Pathogenic Mutation ◽  
The Other ◽  
Loss Of Function ◽  
Case Presentation ◽  
Carbamazepine Therapy ◽  
Myoclonus Dystonia ◽  
Back Ward

Abstract Background Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE). Case presentation We here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up. Conclusions Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.

scholarly journals Genetic Determinants Of Clinical Phenotype In Hypertrophic Cardiomyopathy 

2020 ◽  
Author(s):  
Lazar Velicki ◽  
Djordje G Jakovljevic ◽  
Andrej Preveden ◽  
Miodrag Golubovic ◽  
Marija Bjelobrk ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Clinical Phenotype ◽  
Genetic Disorder ◽  
Positive Family History ◽  
Mitral Annulus ◽  
Genetic Determinants ◽  
Myosin Binding Protein ◽  
Number Of Patients ◽  
History Of ◽  
The Difference

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.Methods: As a part of the international multidisciplinary SILICOFCM project (www.silicofcm.eu) the present study evaluated the association between underlying genetic mutations and clinical phenotype in patients with HCM. Only patients with confirmed single pathogenic mutations in either MYBPC3 or MYH7 genes were included in the study and divided into two groups accordingly. The MYBPC3 group was comprised of 48 patients (76%), while the MYH7 group included 15 patients (24%). Each patient underwent clinical examination and echocardiography.Results: The most prevalent symptom in patients with MYBPC3 was dyspnea (44%), whereas in patients with MYH7 it was palpitations (33%). The MYBPC3 group had a significantly higher number of patients with a positive family history of HCM (46% vs. 7%; p=0.014). There was a numerically higher prevalence of atrial fibrillation in the MYH7 group (60% vs. 35%, p=0.085). Laboratory analyses revealed normal levels of creatinine (85.5±18.3 vs. 81.3±16.4 µmol/l; p=0.487) and blood urea nitrogen (10.2±15.6 vs. 6.9±3.9 mmol/l; p=0.472) which were similar in both groups. The systolic anterior motion presence was significantly more frequent in patients caring MYH7 mutation (33% vs. 10%; p=0.025), as well as mitral leaflet abnormalities (40% vs. 19%; p=0.039). Calcifications of mitral annulus were registered only in MYH7 patients (20% vs. 0%; p=0.001). The difference in diastolic function, i.e. E/e’ ratio between the two groups was also noted (MYBPC3 8.8±3.3, MYH7 13.9±6.9, p=0.079).Conclusions: Major findings of the present study corroborate the notion that MYH7 gene mutation patients are presented with more pronounced disease severity than those with MYBPC3.

scholarly journals Screening of Mutations and Polymorphisms in the Glucokinase Gene in Czech Diabetic and Healthy Control Populations

2008 ◽  
pp. S99-S108
Author(s):  
P Lukášová ◽  
J Včelák ◽  
M Vaňková ◽  
D Vejražková ◽  
K Andělová ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Pathogenic Mutation ◽  
Glucokinase Gene ◽  
Exon 2 ◽  
Patients With Diabetes ◽  
Healthy Control ◽  
History Of ◽  
And Control ◽  
Flanking Regions

Glucokinase (GCK) plays a key role in glucose metabolism. GCK mutations are known as a pathogenic cause of maturity-onset diabetes of the young type 2 (MODY2). These mutations are also found in gestational diabetics. The aim of our study was to assess the variability of the GCK gene in the Czech diabetic and control populations. We screened all 10 exons specific for the pancreatic isoform of glucokinase (1a and 2-10) including the intron flanking regions in 722 subjects (in 12 patients with an unrecognised type of MODY and their 10 family members, 313 patients with diabetes mellitus type 2 (DM2), 141 gestational diabetics (GDM), 130 healthy offspring of diabetic parents, and 116 healthy controls without family history of DM2). In two MODY families we identified two mutations in exon 2 of the GCK gene: a novel mutation Val33Ala and the previously described mutation Glu40Lys. In other subgroups (excluding MODY families) we detected only intronic variants and previously described polymorphisms in exons 6 (Tyr215Tyr) and 7 (Ser263Ser), we did not find any known GCK pathogenic mutation. We observed no difference in the frequencies of GCK polymorphisms between Czech diabetic (DM2, GDM) and non-diabetic populations.

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