Posts Categorized: Part 28: NEUROGENETICS



Did the neuron evolve twice?

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Due to its complexity, the neuron as a specialized cell is assumed to have evolved only once in the history of life. However, the information from the newly sequenced genome of a comb jelly appears to suggest otherwise. Based on their DNA data these invertebrates were classified on a different, older branch of the tree of […]



Mechanism for neurexin, neuroligin in synaptic function?

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Mutations in neurexin and neuroligin (synaptic adhesion molecules) have been linked to autism and schizophrenia in humans. The mechanism by which defects in these molecules affect synaptic function and development has not been obvious. Hu et al. (Science, 2012) found that in Caenorhabditis elegans neurexin and neuroligin mediate a retrograde synaptic signal that inhibits neurotransmitter […]



Diagnostic exome sequencing in intellectual disability.

Posted by & filed under Exome sequencing, Part 06: DIAGNOSTIC APPROACHES, Part 28: NEUROGENETICS, Tools.

de Ligt et al. evaluated patients with intellectual disability to exclude known causes and then sequenced the coding regions of more than 21,000 genes obtained from 100 patients with an IQ below 50 and their unaffected parents. The total diagnostic yield was 16%, mostly involving de novo mutations. The authors conclude that de novo mutations […]



Vanishing White Matter Disease

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I recently saw a very young patient in whom I made a diagnosis of Vanishing White Matter Disease (VWMD). This is a leukoencephalopathy caused by mutations in one of the subunits of eukaryotic initiation factor eIF2B, which plays an important role in regulation of protein synthesis in stress conditions. The family of this child wanted to know if […]



Biomarkers for AD Alzheimer’s Disease

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Bateman et al. performed a prospective, longitudinal study about Autosomal dominant Alzheimer’s disease. 128 participants went through baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. Cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset were conducted in order to determine the relative order and […]



APP variant protective against Alzheimer’s disease

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Alzheimer’s disease is characterized by amyloid plaques formed via cleavage of amyloid precursor protein (APP). Jonsson et al. studied coding variants in APP gene in a set of whole-genome sequence data from 1,795 Icelanders, searching for low-frequency variants in APP gene with a significant effect on the risk of Alzheimer’s disease. A coding mutation (A673T) […]



Targeting nuclear RNA for in vivo correction of myotonic dystrophy.

Posted by & filed under Part 25: MUSCLE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT, Treatment.

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder characterized by myotonia, weakness, cardiac arrhythmias, diabetes and cognitive deficits. Patients carry an expansion of the CTG DNA repeat sequence in the DMPK gene. As a result, when the mutant gene is expressed, it yields a toxic messenger RNA molecule (a gain-of-function effect). In addition […]



Cholesterol-enriched diet for treatment of Pelizaeus-Merzbacher disease

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A letter recently published in Nature Medicine reports the role of diet enriched in cholesterol for treatment of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy due to increased dosage of the gene encoding the proteolipid protein 1 (PLP1) . The major finding of this study is that cholesterol promotes normal trafficking of PLP and PMD mice […]



Autism

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Campbell and colleagues found through a GWAS a significant association of autism spectrum disorder (ASD) with a SNP located in a gene-poor region of chromosome 5p14.1. They found that individuals who carry this ASD-associated SNP showed increased expression of  moesin pseudogene 1, antisense(MSNP1AS), a noncoding RNA encoded by the moesin pseudogene 1 (MSNP1). MSNP1AS is […]



Mutations in histone acetyltransferase KAT6B cause Genitopatellar syndrome.

Posted by & filed under Exome sequencing, Part 22: CONNECTIVE TISSUE, Part 28: NEUROGENETICS, Part 30: MULTISYSTEM INBORN ERRORS OF DEVELOPMENT.

Sorry to blow my own horn but I’m quite passionate about the findings described below. Late last year, the group of Clayton-Smith et al. identified mutations in KAT6B in Ohdo syndrome, a condition characterized by blepharophimosis and developmental delay. Shortly after, our group and the group of Simpson et al. identified mutations in the same […]