A5024888121- Hereditary Neurological Disorders
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- RNA regulation and disease
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- Wnt/β-catenin signaling in development and cancer
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Fibromyalgia and Chronic Fatigue Syndrome Research
Oslo University Hospital
2012-2022
University of Oslo
2012-2020
Abstract GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) complex and facilitates formation small nuclear ribonucleoproteins (snRNPs), building blocks spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, cerebellar ataxia harboring biallelic variants in GEMIN5 gene. Mutations perturb subcellular distribution, stability, expression its interacting partners patient...
Hereditary ataxia and spastic paraplegia are heterogeneous monogenic neurodegenerative disorders. To date, a large number of individuals with such disorders remain undiagnosed. Here, we have assessed molecular diagnosis by gene panel sequencing in 105 early late-onset hereditary probands, whom extensive previous investigations had failed to identify the genetic cause disease. Pathogenic likely-pathogenic variants were identified 20 probands (19%) uncertain significance ten (10%). Together...
Background and purpose Hereditary spastic paraplegias (HSPs) are clinically genetically heterogeneous monogenic disorders. To date, nearly 70 genes known to be causative. The aim of this project was identify the genetic cause autosomal dominantly inherited pure HSP in two large, unrelated non‐consanguineous families. Methods families were characterized selected members underwent whole exome sequencing. Potentially disease‐causing variants confirmed by Sanger sequencing their functional...
Recessive loss of function the neuronal ubiquitin hydrolase UCHL1 has been implicated in early-onset progressive neurodegeneration (MIM no. 615491), so far only one family. In this study a second family is characterized, and functional consequences identified mutations are explored. Three siblings developed childhood-onset optic atrophy, followed by spasticity ataxia. Whole exome sequencing compound heterozygous variants UCHL1, c.533G > A (p.Arg178Gln) c.647C (p.Ala216Asp), cosegregating...
The hereditary ataxias are a heterogenous group of disorders with an increasing number causative genes being described. Due to the clinical and genetic heterogeneity seen in these conditions, majority such individuals endure diagnostic odyssey or remain undiagnosed. Defining molecular etiology can bring insights into responsible pathways eventually identification therapeutic targets. Here, we describe biallelic variants
Background and purpose SPG 7 is one of the most common forms autosomal recessive hereditary spastic paraplegia. The phenotype has been shown to be heterogeneous, varying from a complex ataxia pure paraplegia or ataxia. aim this study was clinically genetically characterize patients with in Norway. Methods Six Norwegian families clinical diagnosis were diagnosed through Sanger sequencing whole‐exome sequencing. Haplotypes established identify possible founder mutation. All thoroughly examined...
A family with homocarnosinosis was reported in the literature 1976. Three affected siblings had spastic paraplegia, retinitis pigmentosa, mental retardation, and cerebrospinal fluid (CSF) homocarnosine concentrations 20 times higher than controls. Based on clinical findings new genetic techniques, we have been able to establish a precise diagnosis.The medical records were re-evaluated, analyses performed post-mortem this original family. SNP array-based whole genome homozygosity mapping...
Spastic paraplegia type 5 (SPG5/HSP-CYP7B1) is an autosomal recessive hereditary spastic (HSP) caused by biallelic variants in the CYP7B1 gene, resulting dysfunction of enzyme oxysterol-7-α-hydroxylase. The consequent accumulation hydroxycholesterols plasma seems to be pathognomonic for SPG5, and represent a possible target treatment. We aimed characterize Norwegian patients with including clinical examinations, genetic analyses, measurements hydroxycholesterols, electrophysiological...