scholarly journals Two Novel KCNQ2 Mutations in 2 Families With Benign Familial Neonatal Convulsions

2017 ◽  
Vol 4 ◽  
pp. 2329048X1769139 ◽  
Author(s):  
Ghalia Al Yazidi ◽  
Michael I. Shevell ◽  
Myriam Srour
Keyword(s):  
Phenotypic Variability ◽  
Intermediate Phenotype ◽  
Psychomotor Development ◽  
Epilepsy Syndrome ◽  
Missense Mutations ◽  
Clinical Presentations ◽  
Gated Channel ◽  
Neonatal Convulsions ◽  
History Of ◽  
Intrafamilial Phenotypic Variability

Benign familial neonatal convulsion is a rare autosomal dominant inherited epilepsy syndrome characterized by unprovoked seizures in the first few days of life, normal psychomotor development, and a positive intergenerational family history of neonatal seizures. Over 90% of the affected individuals have inherited causal mutations in KCNQ2, which encodes for the potassium voltage-gated channel subfamily Q, member 2. Mutations in KCNQ2 are also associated with a severe neonatal encephalopathy phenotype associated with poor seizure control and neurodevelopmental deficits. The authors report the clinical presentations, response to medication, and intrafamilial phenotypic variability in 2 families with benign familial neonatal convulsions, carrying previously unreported heterozygous missense mutations, c.1066C>G (p.Leu356Val) and c.1721G<A (p.Gly574Asp), in KCNQ2. The cases reported herein suggest that inherited missense mutations in KCNQ2 can be associated with an intermediate phenotype and illustrate the challenges associated with prognosis and counselling for individuals with inherited missense mutations in KCNQ2.

Recognizing Atypical Dopa-Responsive Dystonia and Its Mimics

2021 ◽  
pp. 10.1212/CPJ.0000000000001125
Author(s):  
Philippe A. Salles ◽  
Mérida Terán-Jimenez ◽  
Alvaro Vidal-Santoro ◽  
Pedro Chaná-Cuevas ◽  
Marcelo Kauffman ◽  
...  
Keyword(s):  
Lower Limb ◽  
Late Onset ◽  
Phenotypic Variability ◽  
Poor Response ◽  
Diurnal Fluctuation ◽  
Oculogyric Crisis ◽  
Sleep Benefit ◽  
History Of ◽  
Non Motor Symptoms ◽  
Intrafamilial Phenotypic Variability

ABSTRACTPurpose of ReviewDopa-responsive dystonia (DRD) encompasses a group of phenotypically and genetically heterogeneous neurochemical disorders. Classic GTP cyclohydrolase 1 (GCH-1)-associated DRD consists of early-onset lower limb asymetrical dystonia, with sleep benefit, diurnal variation, and excellent and sustained response to low L-dopa doses.Recent findingsUnlike the classic phenotype, GCH-1-associated DRD may include features inconsistent with the original phenotype. We describe a GCH-1-associated late-onset DRD case with family history of parkinsonism and cervical dystonia whose response to levodopa was poor and complicated with dyskinesia, blepharospasm and severe non-motor symptoms. We use this case as a springboard to review the spectrum of atypical DRD, DRD-plus and DRD mimics.SummaryGCH-1-related dystonia may exhibit wide intrafamilial phenotypic variability, no diurnal fluctuation, poor response to L-dopa, and such complications as dyskinesia, epilepsy, sleep disorders, autonomic dysfunction, oculogyric crisis, myoclonus, or tics. More recently, rare GCH-1 variants have been found to be associated with Parkinson's disease. Clinicians should be aware of atypical DRD, DRD-plus and DRD mimics.

Formation and composition of training flax collection

2020 ◽  
pp. 61-71
Author(s):  
L.M. Kryvosheieva ◽  
V.I. Chuchvaha ◽  
N.M. Kandyba
Keyword(s):  
Plant Breeding ◽  
Gene Pool ◽  
Phenotypic Variability ◽  
Plant Genetic Resources ◽  
Field Measurements ◽  
Educational Process ◽  
Educational Institutions ◽  
Economic Traits ◽  
Wide Range ◽  
History Of

Aim. Based on the results of multi-year research into the flax gene pool, to form a flax training collection to provide breeding scientific organizations and educational institutions with collection samples as well as with information about the bast crop gene pool. Results and Discussion. The studies were conducted in the crop rotation fields for breeding and seed production of the Institute of Bast Crops of the NAAS (Hlukhiv, Sumska Oblast) in 1992-2018. The field measurements and laboratory analyses were carried out in accordance with conventional methods of field and laboratory studies of collection flax samples.The article presents the results on the formation of a training collection of flax at the Institute of Bast Crops of the NAAS, which has 117 accessions (11 botanical species and three varieties) from 22 countries. In addition to species diversity, the collection includes accessions with different levels of expression of valuable economic and biological characteristics. It also includes accessions selected by phenotypic variability of individual characters or their combinations. The multi-year research into the flax collection accessions resulted in identification of sources of highly-expressed valuable economic traits, which are of interest for the plant breeding course. The history of flax breeding in Ukraine is shown, where breeding varieties that are most widespread or were significant breeding achievements in solving certain problems, are presented. The collection can be used as a visual aid for the plant breeding course in educational programs; in addition, it can provide starting material for scientific and educational institutions. The collection is registered with the National Center for Plant Genetic Resources of Ukraine (certificate No. 00273 dated 04/11/2019). Conclusions. The studies of accessions from the national flax collection allowed us to build up a training collection and register it with the NCPGRU. The collection represents a wide range of biological and economic features of the gene pool of this crop. The collection can be used in the educational process of educational agricultural and biological institutions. The multi-year research into the national flax collection resulted in identification of sources of highly-expressed valuable economic traits, which are of interest to the plant breeding course. The history of flax breeding in Ukraine got covered, and breeding varieties that are most widespread or were significant breeding achievements in solving certain problems are presented.

A Brief History of Psoriasis Management in Canada

2020 ◽  
Vol 24 (3) ◽  
pp. 273-277
Author(s):  
Khalad Maliyar ◽  
Patrick Fleming ◽  
Boluwaji Ogunyemi ◽  
Charles Lynde
Keyword(s):  
20Th Century ◽  
Coal Tar ◽  
Historical Review ◽  
Chronic Inflammatory Disease ◽  
Biologic Therapies ◽  
First Line ◽  
Revolutionary Change ◽  
Clinical Presentations ◽  
History Of ◽  
The 19Th Century

Psoriasis is a chronic, inflammatory disease with a varying degree of clinical presentations. Managing psoriasis has always been arduous due to its chronicity and its propensity to relapse. Prior to the development of targeted biologic therapies, there were few effective treatments for psoriasis. Ancient psoriasis therapies included pinetar, plant extracts, psychotherapy, arsenic, and ammoniated mercury. In the 19th century, chrysarobin was developed. Then, in the early half of the 20th century, anthralin and coal tar were in widespread use. In the latter half of the 20th century, treatments were limited to topical first-line therapies, systemic drugs, and phototherapy. However, as the treatment of psoriasis has undergone a revolutionary change with the development of novel biologic therapies, patients with moderate to severe psoriasis have been able to avail therapies with high efficacy and durability along with an acceptable safety profile. This article is a brief historical review of the management of psoriasis prior to the inception of biologics and with the development of novel biologic therapies.

scholarly journals The natural history of Canavan disease: 23 new cases and comparison with patients from literature

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Annette Bley ◽  
Jonas Denecke ◽  
Alfried Kohlschütter ◽  
Gerhard Schön ◽  
Sandra Hischke ◽  
...  
Keyword(s):  
Severity Score ◽  
Canavan Disease ◽  
Psychomotor Development ◽  
Rank Test ◽  
First Year ◽  
Study Cohort ◽  
Pooled Data ◽  
Kaplan Meier ◽  
History Of ◽  
First Year Of Life

Abstract Background Canavan disease (CD, MIM # 271900) is a rare and devastating leukodystrophy of early childhood. To identify clinical features that could serve as endpoints for treatment trials, the clinical course of CD was studied retrospectively and prospectively in 23 CD patients. Results were compared with data of CD patients reported in three prior large series. Kaplan Meier survival analysis including log rank test was performed for pooled data of 82 CD patients (study cohort and literature patients). Results Onset of symptoms was between 0 and 6 months. Psychomotor development of patients was limited to abilities that are usually gained within the first year of life. Macrocephaly became apparent between 4 and 18 months of age. Seizure frequency was highest towards the end of the first decade. Ethnic background was more diverse than in studies previously reported. A CD severity score with assessment of 11 symptoms and abilities was developed. Conclusions Early hallmarks of CD are severe psychomotor disability and macrocephaly that develop within the first 18 months of life. While rare in the first year of life, seizures increase in frequency over time in most patients. CD occurs more frequently outside Ashkenazi Jewish communities than previously reported. Concordance of phenotypes between siblings but not patients with identical ASPA mutations suggest the influence of yet unknown modifiers. A CD severity score may allow for assessment of CD disease severity both retrospectively and prospectively.

scholarly journals The Contursi Family 20 Years Later: Intrafamilial Phenotypic Variability of the SNCA p.A53T Mutation

2016 ◽  
Vol 31 (2) ◽  
pp. 257-258 ◽  
Author(s):  
Lucia Ricciardi ◽  
Simona Petrucci ◽  
Daniela Di Giuda ◽  
Laura Serra ◽  
Barbara Spanò ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Intrafamilial Phenotypic Variability

Marriage, monogamy and HIV: a profile of HIV-infected women in south India

2000 ◽  
Vol 11 (4) ◽  
pp. 250-253 ◽  
Author(s):  
S Newmann ◽  
P Sarin ◽  
N Kumarasamy ◽  
E Amalraj ◽  
M Rogers ◽  
...  
Keyword(s):  
Risk Factor ◽  
Hiv Risk ◽  
South India ◽  
Reproductive Age ◽  
Indian Women ◽  
Clinical Presentations ◽  
Vertical Transmission Of Hiv ◽  
History Of ◽  
The Mean ◽  
Heterosexual Sex

A retrospective study was conducted on 134 HIV-infected females evaluated at an HIV/AIDS centre in south India to characterize their socio-demographics, HIV risk factors and initial clinical presentations. The mean age was 29 years; 81% were housewives; 95% were currently or previously married; 89% reported heterosexual sex as their only HIV risk factor; and 88% reported a history of monogamy. The majority were of reproductive age, thus the potential for vertical transmission of HIV and devastating impacts on families is alarming. Nearly half of these women initially presented asymptomatically implying that partner recruitment can enable early HIV detection. Single partner heterosexual sex with their husband was the only HIV risk factor for the majority of women. HIV prevention and intervention strategies need to focus on married, monogamous Indian women whose self-perception of HIV risk may be low, but whose risk is inextricably linked to the behaviour of their husbands.

scholarly journals FLT4 Mutations Are Associated with Segmental Lymphatic Dysfunction and Initial Lymphatic Aplasia in Patients with Milroy Disease

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1611
Author(s):  
Ningfei Liu ◽  
Minzhe Gao
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Clinical Signs ◽  
Lymphatic Vessels ◽  
Growth Factor Receptor ◽  
Kinase Domain ◽  
Tyrosine Kinase Domain ◽  
Missense Mutations ◽  
History Of ◽  
Endothelial Growth Factor

This study explored mutations in the Fms-related tyrosine kinase 4/vascular endothelial growth factor receptor 3 gene (FLT4) and lymphatic defects in patients with Milroy disease (MD). Twenty-nine patients with lower limb lymphedema were enrolled. Sixteen patients had a familial history of MD, while 13 patients exhibited sporadic MD. Clinical signs, FLT4 mutations, indocyanine green (ICG) lymphography findings, and skin tissue immunohistochemical staining results were evaluated. Twenty-eight variants in FLT4 were identified. Twelve of these have previously been reported, while 16 are novel. Of the 28 variants, 26 are missense mutations, and the remaining two comprise a splicing mutation and a non-frame shift mutation. Twenty-five variants are located in the intracellular protein tyrosine kinase domain; three are located in the extracellular immunoglobulin domain. Substantially delayed contrast-enhanced tortuous lymphatic vessels were visualized to the ankle or knee level in 15 of 23 patients who underwent ICG lymphography. No initial lymphatic vessels were visualized in skin specimens from four patients who did not exhibit lymphatic vessels during imaging analyses. No specific variant was identified in relation to the unique clinical phenotype. Segmental dysfunction of lymphatic vessels and initial lymphatic aplasia are present in MD patients with FLT4 mutations.

Striking intrafamilial phenotypic variability and spastic paraplegia in the presence of similar homozygous expansions of theFRDA1gene

2004 ◽  
Vol 19 (12) ◽  
pp. 1424-1431 ◽  
Author(s):  
AmanPreet Badhwar ◽  
An Jansen ◽  
Frederick Andermann ◽  
Massimo Pandolfo ◽  
Eva Andermann
Keyword(s):  
Phenotypic Variability ◽  
Spastic Paraplegia ◽  
Intrafamilial Phenotypic Variability

scholarly journals Tumour risks and genotype–phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD

2018 ◽  
Vol 55 (6) ◽  
pp. 384-394 ◽  
Author(s):  
Katrina A Andrews ◽  
David B Ascher ◽  
Douglas Eduardo Valente Pires ◽  
Daniel R Barnes ◽  
Lindsey Vialard ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Phenotypic Variability ◽  
Cohort Analysis ◽  
Cumulative Risk ◽  
Clinical Information ◽  
Missense Mutations ◽  
Pathogenic Variants ◽  
Mutation Carriers ◽  
Kaplan Meier ◽  
Age Related

BackgroundGermline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype–phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers.MethodsA retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses.ResultsTumour risks analysis provided novel penetrance estimates and genotype–phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%).ConclusionsOverall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype–tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers.

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