scholarly journals Looking “Cherry Red Spot Myoclonus” in the Eyes: Clinical Phenotype, Treatment Response, and Eye Movements in Sialidosis Type 1

2021 ◽  
Vol 11 (1) ◽  
pp. 53
Author(s):  
Giulietta M. Riboldi ◽  
John Martone ◽  
John-Ross Rizzo ◽  
Todd E. Hudson ◽  
Janet C. Rucker ◽  
...  
Keyword(s):  
Eye Movements ◽  
Treatment Response ◽  
Clinical Phenotype ◽  
Cherry Red Spot

Clinical Features of Infantile GM1 Gangliosidosis: Report of an Iranian Patient

2020 ◽  
Author(s):  
Mahtab Ordooei ◽  
Razieh Fallah ◽  
Fatemeh Abdi ◽  
Fahimeh Soheilipour
Keyword(s):  
Lysosomal Storage ◽  
Gm1 Gangliosidosis ◽  
Case Presentation ◽  
Iranian Patient ◽  
Cherry Red Spot ◽  
Type 3 ◽  
Initial Check ◽  
Infantile Type

Background: GM1 gangliosidosis is an autosomal recessive lysosomal storage disease due to a lack of β-galactosidase activity, exactly because of mutations in the GLB1 gene. GM1 gangliosidosis is a rare disease that could occur either during infancy (infantile type 1), as a juvenile (type 2), or in adulthood (type 3) in both nervous and skeletal systems. Type 1 is characterized by premature psychomotor deterioration, visceromegaly, macular cherry-red spot, skeletal deformities, and death in the first 2 years of life. Case Presentation: We reported an Iranian infant who, on initial check-up, had coarse face, visceromegaly, dystonia, and hepatosplenomegaly that increased at 15 months of age. At the initial check-up, a genetic test was performed and GM1 gangliosidosis type 1 was diagnosed. Conclusion: infant form is characterized by early-onset before the age of 6 months and rapidly progressive psychomotor deterioration, facial abnormalities, and visceromegaly.

scholarly journals Patients with Advanced HIV Type 1 Infection Initiating Antiretroviral Therapy in Botswana: Treatment Response and Mortality

2009 ◽  
Vol 25 (2) ◽  
pp. 127-133 ◽  
Author(s):  
Andrew Mujugira ◽  
C. William Wester ◽  
Soyeon Kim ◽  
Hermann Bussmann ◽  
Tendani Gaolathe
Keyword(s):  
Antiretroviral Therapy ◽  
Treatment Response ◽  
Hiv Type 1

Optokinetic nystagmus in patients with SCA

Neurology ◽  
2018 ◽  
Vol 91 (13) ◽  
pp. e1255-e1261 ◽  
Author(s):  
Doniparthi V. Seshagiri ◽  
Pramod Kumar Pal ◽  
Sanjeev Jain ◽  
Ravi Yadav
Keyword(s):  
Eye Movements ◽  
Prospective Observational Study ◽  
Rating Scale ◽  
Optokinetic Nystagmus ◽  
Neurologic Examination ◽  
Clinical Tool ◽  
Motor Disability ◽  
Tendon Reflexes ◽  
Sensitive Marker

ObjectiveTo characterize the clinical features in patients with spinocerebellar ataxia (SCA) type 1, SCA2, and SCA3 and to evaluate the oculomotor dysfunction by using optokinetic nystagmus (OKN) testing, which may be a sensitive marker.MethodsIn this prospective observational study, all patients underwent detailed neurologic examination with special emphasis on eye movements. OKN was evaluated with a tape. Disease severity was measured with the International Co-Operative Ataxia Rating Scale (ICARS).ResultsA total of 73 genetically confirmed patients were included, of whom 28, 30, and 15 patients were positive for SCA1, SCA2, and SCA3, respectively. Dystonia was more common in patients with SCA3 (46%), and absent ankle jerk was more common in those with SCA2 (21.4%). Brisk deep tendon reflexes were common in patients with SCA1 (46.6%), followed by patients with SCA3 (26.6%) and SCA2 (7.1%). Vertical OKN was impaired in all patients and absent in 86.6% of patients with SCA1, 96% of those with SCA2, and 80% of those with SCA3. Horizontal OKN was absent in 30% of patients with SCA1, 57% of patients with SCA2, and 33% of those with SCA3. Higher motor disability (posture and gait, kinetic functions [Motor Disability] subscore on the ICARS) was associated with higher oculomotor dysfunction measured by OKN-saccades impairment grading but not with the Ocular Disorder subscore of ICARS (ICARS-OD).ConclusionOKN-saccades are a better and sensitive bedside clinical tool to quantify oculomotor dysfunction in neurodegenerative ataxias. Its role needs to be tested further in presymptomatic carriers. The current ICARS-OD scale to grade oculomotor dysfunction in degenerative ataxias need to be modified.

Mutation Type As a Major Determinant of Clinical Phenotype in Myeloproliferative Neoplasms Associated with Mutant Calreticulin

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3215-3215 ◽  
Author(s):  
Daniela Pietra ◽  
Elisa Rumi ◽  
Chiara Milanesi ◽  
Christian A Di Buduo ◽  
Marta Bellini ◽  
...  
Keyword(s):  
Amino Acids ◽  
Clinical Phenotype ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Charged Amino Acids ◽  
Calr Mutations ◽  
Mutation Type ◽  
Calr Mutation

Abstract About 25% of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF) carry a somatic mutation of CALR, the calreticulin gene [N Engl J Med. 2013;369:2379-90]. So far, more than 50 different indels in CALR exon 9 have been found, but a 52-bp deletion (type 1 mutation) and a 5-bp insertion (type 2) are the most common lesions. All indels generate a novel C-terminus of the mutant protein, in which the endoplasmic reticulum retention signal KDEL is lost and the negatively charged amino acids are replaced by neutral and positively charged amino acids, disrupting the Ca-binding site. This suggests that both cellular dislocation and impaired Ca-binding activity may be involved in the abnormal proliferation of cells expressing a mutant calreticulin. It is still unclear, however, why the same mutant gene is associated with 2 different disease phenotypes (ET and PMF). In particular, little in known about the effect of the mutant protein on megakaryocyte biology and bone marrow collagen deposition. We studied the relationships between CALR mutation type, megakaryocyte biology, and clinical phenotype in patients with myeloproliferative neoplasms. According to the 2008 WHO criteria, 716 out of 892 patients had ET and 176 had PMF. Overall, 578 (65%) patients carried JAK2 (V617F), 230 (26%) had a CALR indel, and 84 (9%) had nonmutated JAK2 and CALR. Patients with MPL mutations were excluded. Twenty-six different types of CALR lesions were identified: 120 (52%) patients had type 1 mutation, 75 (33%) had type 2, and 35 (15%) carried other indels. The frequency of type 1 mutation was significantly higher in PMF than in ET (71% vs 46%, P=.004). All these variants involved 3 different stretches of negatively charged amino acids, with an increase in the isoelectric points (pI) of the mutant protein. As type 1 and type 2 mutations affected stretch I and III, respectively, the 26 indels were categorized into 3 groups on the basis of the stretch they affected: i) type 1-like (61%), affecting stretch I; ii) type 2-like (36%), stretch III; iii) and other types (3%), stretch II. The pI values were significantly different in the 3 groups (P<.001). The frequency of type-1 like mutations was significantly higher in PMF than in ET (82% vs 55%, P=.001). In vitro differentiated megakaryocytes from CALR-mutant patients displayed a significant increase in the extent of both intracellular Ca2+ release from the endoplasmic reticulum and extracellular Ca2+ entry inside the cytoplasm, as compared with healthy controls. Megakaryocytes carrying type 1-like CALR mutations exhibited the highest amplitude of Ca2+ flows regardless of the type of disease. In ET, impaired Ca2+ homeostasis was accompanied by atypical proplatelet architecture (ie, more branches and bifurcations). With respect to clinical phenotype at diagnosis, ET patients with type 2-like CALR mutation showed a trend towards higher PLT count (P=.063) and lower age (P=.053), and significantly lower LDH values (P=.021) than those with type 1-like mutation. In a hierarchical cluster analysis including demographic, clinical and molecular data, CALR mutation type (1 vs 2) identified the 2 clusters with the highest dissimilarity. Considering all patients, those with type 2-like CALR lesions had a better survival than those with JAK2 (V617F) (96.1% vs 84.4% at 10 years, P=.039), while no difference was found between the 2 CALR mutation types. ET patients with type 2-like CALR mutations showed a lower risk of thrombosis than those with JAK2 (V617F) (P=.010). By contrast, ET patients with type 1-like CALR mutations had a higher risk of myelofibrotic transformation that those with type 2-like CALR mutations (P=.029) and especially those with JAK2 (V617F) (P=.011). Finally, PMF patients with type 1-like CALR variants had a better survival than those with JAK2 (V617F) (80.1% vs 48% at 10 years, P=.008). In summary, abnormalities in megakaryocyte calcium metabolism and proplatelet architecture are found in patients with CALR-mutant myeloproliferative neoplasms, and their extent is related to mutation type. Type 2-like CALR mutations are more likely to be associated with isolated thrombocytosis without bone marrow fibrosis, ie, with an ET phenotype. By contrast, type 1-like CALR mutations are generally associated with bone marrow fibrosis, ie, with a PMF phenotype. Thus, in CALR-mutant myeloproliferative neoplasms, the mutation type is a major determinant of the clinical phenotype. Disclosures No relevant conflicts of interest to declare.

scholarly journals Higher Risk of Aggressive Pancreatic Neuroendocrine Tumors in MEN1 Patients With MEN1 Mutations Affecting the CHES1 Interacting MENIN Domain

2014 ◽  
Vol 99 (11) ◽  
pp. E2387-E2391 ◽  
Author(s):  
Detlef K. Bartsch ◽  
Emily P. Slater ◽  
Max Albers ◽  
Richard Knoop ◽  
Brunhilde Chaloupka ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Clinical Phenotype ◽  
Tertiary Referral ◽  
Course Of Disease ◽  
Tertiary Referral Center ◽  
Checkpoint Kinase 1 ◽  
Related Mortality

Context: Sixty to 80% of multiple endocrine neoplasia type 1 (MEN1) patients develop pancreatic neuroendocrine neoplasias (pNENs), which reveal an aggressive behavior in 10%-20% of patients. Causative MEN1 mutations in the interacting domains of the encoded Menin protein directly alter its regulation abilities and may influence the phenotype. Objective: The objective of the study was the evaluation of an association between MEN1 mutations in different interacting domains of Menin and the phenotype of pNENs. Design: This was a retrospective analysis of a prospectively collected cohort of 71 genetically confirmed MEN1 patients at a tertiary referral center. Main Outcome Measures: Analysis of patients' characteristics and clinical phenotype of pNENs regarding the mutation type and its location in Menin interacting domains was measured. Results: Sixty-seven patients (93%) developed pNENs after a median follow-up of 134 months. Patients with mutations leading to loss of interaction (LOI) with the checkpoint kinase 1 (CHES1) interacting domain codons (428–610) compared with patients with mutations resulting in LOI with other domains (eg, JunD, Smad3) had significantly higher rates of functioning pNENs (70% vs 34%), malignant pNENs (59% vs 16%), and aggressive pNENs (37% vs 9%), respectively. Patients with CHES1-LOI also had an increased pNEN-related mortality (20% vs 4.5%). Neither gender, age, nor the ABO blood types were associated with the phenotype of pNENs. Conclusions: MEN1 patients with MEN1 mutations leading to CHES1-LOI have a higher risk of malignant pNENs with an aggressive course of disease and disease-related death.

Mosaic Generalized Neurofibromatosis 1: Report of Two Cases

2014 ◽  
Vol 18 (4) ◽  
pp. 271-274 ◽  
Author(s):  
Jori Hardin ◽  
Allan Behm ◽  
Richard M. Haber
Keyword(s):  
Somatic Mutations ◽  
Clinical Phenotype ◽  
Neurofibromatosis Type ◽  
Neurofibromatosis 1 ◽  
Limited Disease ◽  
Disease Mutations ◽  
Single Region ◽  
History Of

Background: We report two cases of mosaic generalized neurofibromatosis 1 (NF1) and review the history of the classification of segmental neurofibromatosis (SNF; Ricardi type NF-V). Somatic mutations giving rise to limited disease, such as segmental neurofibromatosis are manifestations of mosaicism. If the mutation occurs before tissue differentiation, the clinical phenotype will be generalized disease. Mutations that occur later in development give rise to disease that is confined to a single region. Objectives: Segmental neurofibromatosis is caused by a somatic mutation of neurofibromatosis type 1, and should not be regarded as a distinct entity from neurofibromatosis 1. Cases previously referred to as unilateral or bilateral segmental neurofibromatosis are now best referred to as mosaic generalized or mosaic localized neurofibromatosis 1.

Risk Prediction for Clinical Phenotype in Myotonic Dystrophy Type 1: Data from 2,650 Patients

2007 ◽  
Vol 11 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Leila Baghernajad Salehi ◽  
Emanuela Bonifazi ◽  
Enrico Di Stasio ◽  
Massimo Gennarelli ◽  
Annalisa Botta ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Risk Prediction ◽  
Clinical Phenotype ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type
Sign in / Sign up

Export Citation Format

Share Document