scholarly journals Autosomal-dominant early-onset spastic paraparesis with brain calcification due to IFIH1 gain-of-function

2018 ◽  
Vol 39 (8) ◽  
pp. 1076-1080 ◽  
Author(s):  
Lyse Ruaud ◽  
Gillian I. Rice ◽  
Christelle Cabrol ◽  
Juliette Piard ◽  
Mathieu Rodero ◽  
...  
Keyword(s):  
Early Onset ◽  
Autosomal Dominant ◽  
Spastic Paraparesis ◽  
Gain Of Function ◽  
Brain Calcification

The calcilytic NPS2143 rectifies the gain-of-function associated with G-protein [alpha] 11 mutations causing autosomal dominant hypocalcaemia type 2

2014 ◽  
Author(s):  
Valerie Babinsky ◽  
Fadil Hannan ◽  
M Andrew Nesbit ◽  
Sarah Howles ◽  
Jianxin Hu ◽  
...  
Keyword(s):  
G Protein ◽  
Autosomal Dominant ◽  
Gain Of Function

scholarly journals Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Neurogenetics ◽  
2021 ◽  
Author(s):  
Luca Magistrelli ◽  
Roberta Croce ◽  
Fabiola De Marchi ◽  
Chiara Basagni ◽  
Miryam Carecchio ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Case Series ◽  
Dominant Trait ◽  
Autosomal Dominant Trait ◽  
Phenotypic Spectrum ◽  
Primary Familial Brain Calcification ◽  
Psychiatric Disturbances ◽  
Brain Calcification ◽  
Uncertain Significance ◽  
Six Genes

AbstractPrimary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.

A presenilin 1 mutation (Arg278Ser) associated with early onset Alzheimer’s disease and spastic paraparesis

2007 ◽  
Vol 260 (1-2) ◽  
pp. 78-82 ◽  
Author(s):  
Ashok Raman ◽  
Xia Lin ◽  
Mohnish Suri ◽  
Monica Hewitt ◽  
Cris S. Constantinescu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Onset ◽  
Spastic Paraparesis ◽  
Presenilin 1 ◽  
Presenilin 1 Mutation ◽  
Early Onset Alzheimer’S Disease

scholarly journals Gain-of-function mutation in SCN5A causes ventricular arrhythmias and early onset atrial fibrillation

2017 ◽  
Vol 236 ◽  
pp. 187-193 ◽  
Author(s):  
Krystien V. Lieve ◽  
Arie O. Verkerk ◽  
Svitlana Podliesna ◽  
Christian van der Werf ◽  
Michael W. Tanck ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Early Onset ◽  
Ventricular Arrhythmias ◽  
Gain Of Function ◽  
Onset Atrial Fibrillation

scholarly journals Long-Term Outcomes in Patients with Very-Early Onset Autosomal Dominant Polycystic Kidney Disease

2016 ◽  
Vol 44 (3) ◽  
pp. 171-178 ◽  
Author(s):  
Kristen L. Nowak ◽  
Melissa A. Cadnapaphornchai ◽  
Michel B. Chonchol ◽  
Robert W. Schrier ◽  
Berenice Gitomer
Keyword(s):  
Kidney Disease ◽  
Clinical Outcomes ◽  
Polycystic Kidney Disease ◽  
Early Onset ◽  
Autosomal Dominant ◽  
Glomerular Hyperfiltration ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Background: Long-term clinical outcomes in children with very-early onset (VEO; diagnosis in utero or within the first 18 months of life) autosomal dominant polycystic kidney disease (ADPKD) are currently not well understood. We conducted a longitudinal retrospective cohort study to assess the association between VEO status and adverse clinical outcomes. Methods: Seventy patients with VEO-ADPKD matched (by year of birth, sex and race/ethnicity) to 70 patients with non-VEO-ADPKD who participated in research at the University of Colorado were studied. Kaplan-Meier survival analysis was performed. The predictor was VEO status, and outcomes were progression to end-stage renal disease (ESRD), development of hypertension, progression to estimated glomerular filtration rate (eGFR <90 ml/min/1.73 m2), glomerular hyperfiltration (eGFR ≥140 ml/min/1.73 m2) and height-adjusted total kidney volume (htTKV) measured by MRI ≥600 ml/m. Results: Median follow-up was until 16.0 years of age. There were only 4 ESRD events during the follow-up period, all in the VEO group (p < 0.05). VEO patients were more likely to develop hypertension (hazard ratio, HR 3.15, 95% CI 1.86-5.34; p < 0.0001) and to progress to eGFR <90 ml/min/1.73 m2 (HR 1.97, 95% CI 1.01-3.84; p < 0.05) than non-VEO patients. There was no difference between groups in the development of glomerular hyperfiltration (HR 0.89, 95% CI 0.56-1.42; p = 0.62). There were only 7 patients who progressed to htTKV ≥600 ml/m, 4 in the VEO group and 3 in the non-VEO group (p < 0.01). Conclusions: Several clinical outcomes are worse in patients with VEO-ADPKD compared to non-VEO ADPKD. Children with VEO-ADPKD represent a particularly high-risk group of ADPKD patients.

KCNT1-Related Epilepsy: A Review

2021 ◽  
Author(s):  
Valeria Venti ◽  
Lina Ciccia ◽  
Bruna Scalia ◽  
Laura Sciuto ◽  
Carla Cimino ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Unexpected Death ◽  
Gain Of Function ◽  
Nocturnal Frontal Lobe Epilepsy ◽  
Ohtahara Syndrome ◽  
Sodium Dependent ◽  
Cardiac Disorders ◽  
Myoclonic Encephalopathy ◽  
Early Myoclonic Encephalopathy ◽  
Genotype Correlation

Abstract KCNT1 gene encodes the sodium-dependent potassium channel reported as a causal factor for several different epileptic disorders. The gene has been also linked with cardiac disorders and in a family to sudden unexpected death in epilepsy. KCNT1 mutations, in most cases, result in a gain of function causing a neuronal hyperpolarization with loss of inhibition. Many early-onset epileptic encephalopathies related to gain of function of KCNT1 gene have been described, most often associated with two phenotypes: malignant migrating focal seizures of infancy and familial autosomal-dominant nocturnal frontal lobe epilepsy; however, there is no clear phenotype–genotype correlation, in fact same mutations have been represented in patients with West syndrome, Ohtahara syndrome, and early myoclonic encephalopathy. Additional neurologic features include intellectual disability, psychiatric disorders, hypotonia, microcephaly, strabismus, and movement disorders. Conventional anticonvulsant, vagal stimulation, and ketogenic diet have been used in the absence of clinical benefit in individuals with KCNT1-related epilepsy; in some patients, quinidine therapy off-label has been practiced successfully. This review aims to describe the characteristics of the gene, the phenotypes related to genetic mutations with the possible genotype–phenotype correlations and the treatments proposed to date, discussing the comorbidities reported in the literature.

Autosomal Dominant Optic Atrophy

2019 ◽  
pp. 29-34
Author(s):  
Matthew J. Thurtell ◽  
Robert L. Tomsak
Keyword(s):  
Differential Diagnosis ◽  
Optic Atrophy ◽  
Autosomal Dominant ◽  
Spastic Paraparesis ◽  
Progressive External Ophthalmoplegia ◽  
Management Approach ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Autosomal Dominant Optic Atrophy ◽  
Dominant Optic Atrophy ◽  
History Of

There is a broad differential diagnosis for bilateral optic neuropathies, including inflammatory, ischemic, compressive, traumatic, nutritional, toxic, and inherited causes. In this chapter, we begin by discussing the approach to the patient who has bilateral symmetric optic neuropathies. We next review the genetic basis, clinical features, and natural history of autosomal dominant optic atrophy. We list other deficits that can occur in up to 20% of patients with this condition, which can include sensorineural hearing loss, ataxia, myopathy, peripheral neuropathy, spastic paraparesis, and chronic progressive external ophthalmoplegia. Lastly, we discuss the evaluation and management approach for autosomal dominant optic atrophy.

scholarly journals Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification

2020 ◽  
Vol 106 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Lucia V. Schottlaender ◽  
Rosella Abeti ◽  
Zane Jaunmuktane ◽  
Carol Macmillan ◽  
Viorica Chelban ◽  
...  
Keyword(s):  
Early Onset ◽  
Primary Familial Brain Calcification ◽  
Brain Calcification
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