Scientists Designed a Drug for Just One Patient. Her Name Is Mila.
An achievement in ultra-personalized medicine also raises questions about fairness and regulation.
Pathogenic variants in the LONP1 gene have been associated with CODAS syndrome (Cerebral, Ocular, Dental, Auricular, and Skeletal Anomalies Syndrome). A recent report identified the first newborn case with LONP1-related mitochondrial cytopathy due to a compound heterozygous pathogenic variant in LONP1 without features of CODAS. The proband had manifested with severe congenital lactic acidosis and profound multiple respiratory chain complex activity deficiencies associated with the quantitative loss of mtDNA copy number in muscle. A subsequent report identified two siblings with regression during infancy, profound hypotonia...
The gene NGLY1 encodes for a cytosolic enzyme, N-glycanase 1, involved in degradation of N-glycosylated proteins. N-glycanase 1 deficiency was described by Need et al. in 2012 as the first congenital disorder of deglycosylation, and less than thirty cases have been reported since. Hallmark features include autosomal recessive inheritance and a multisystemic disorder. The neurological involvement starts in infancy with hypotonia, ataxia, hyperkinetic movement disorder, seizures and developmental delay/intellectual disability of various degree.
Mutations in the ubiquitin-like modifier activating enzyme 5 (UBA5) gene were recently identified to cause childhood-onset cerebellar ataxia and infantile-onset epileptic encephalopathy, disorders predominantly associated with the central nervous system. Cerebellar ataxia patients show cerebellar atrophy and motor dysfunction; whereas, the clinical symptoms associated with epileptic encephalopathy include reduced motor skills, developmental delay, intellectual disability, microcephaly, delayed brain myelination, and recurrent seizures, ultimately resulting in the death of most patients before the age of twenty.
Rett syndrome is a neurodevelopmental disorder characterized by loss of speech and stereotypic movements. The TRAPPC11 protein is a part of the transport protein particle complex involved in endoplasmic reticulum to Golgi transportation. As more individuals with limb-girdle muscular dystrophy are reported, the spectrum of neurological disorders associated with mutations in the TRAPPC11 gene is beginning to emerge. Infantile hyperkinetic movements, ataxia and intellectual disability have been previously published.
This study aimed to investigate the usefulness of an infrared depth sensor device to quantitatively evaluate gait disturbances in patients with movement disorders. 25 ataxic, 25 Parkinson’s disease, and 25 control subjects were enrolled and evaluated their walk. Stride length, feet interval, gait rhythm, and a ratio of the actual walking route length to the linear distance between the start and goal points (A/L ratio) were assessed and compared. Outcome correlations with clinical scales were also analyzed. The average stride length was shorter in ataxic subjects or Parkinson’s disease subjects than in control s...
This study has focused on verifying the presence of FMR1 expanded alleles since there is a lack of information about this kind of mutation in autism patients from the northern region of Brazil. The presence of large alleles for this gene could offer new therapeutic or pharmacological methods for the treatment of these patients. Both the presence and the frequency of CGG expansions were verified in 90 autism males by molecular analysis. Four of them had intermediate alleles and four others presented premutated alleles. Premutation carriers are on the propensity of developing the late onset Fragile X-associated tremor/ataxia...
This article has an associated First Person interview with the joint first authors of the paper.
We describe a fifth patient, carrying a novel mutation in the same gene, thus confirming the role of TDP2 mutations in determining the disease and defining the main features SCAR23: pediatric onset ataxia and drug-resistant epilepsy and intellectual disability. We further show the clinical presentation which is associated with the neuroradiological evidence of progressive cerebellar atrophy, giving the evidence that SCAR23 can be classified as a degenerative condition. PMID: 31410782 [PubMed - as supplied by publisher]
We describe a fifth patient, carrying a novel mutation in the same gene, thus confirming the role of TDP2 mutations in determining the disease and defining the main features SCAR23: pediatric onset ataxia and drug-resistant epilepsy and intellectual disability. We further show the clinical presentation which is associated with the neuroradiological evidence of progressive cerebellar atrophy, giving the evidence that SCAR23 can be classified as a degenerative condition.
This article is protected by copyright. All rights reserved. PMID: 31353455 [PubMed - as supplied by publisher]