Posts By: Yannis Trakadis

New FRMP gene targets: potential for new treatments in FXS/ASD

Posted by & filed under Part 28: NEUROGENETICS.

Fragile X syndrome (FXS) is typically caused by the loss of fragile X mental retardation 1 (FMR1) expression, which codes for the RNA-binding protein FMRP. Ascano et al. reported the identification of RNA-recognition elements for FMRP, in addition to its target messenger RNAs. Many of FMRP gene targets discovered are involved in brain function and […]

Incidental Findings in Clinical Exome/Genome Sequencing

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

During the Annual Clinical Genetics Meeting of the American College of Medical Genetics and Genomics (ACMG) in Phoenix, the “ACMG Recommendations for Reporting of Incidental Findings in Clinical Exome and Genome Sequencing” were released. This report includes recommendations for management of incidental findings and for a minimum list of conditions, genes, and variants to be […]

Long-term BH4 responsive PKU patients

Posted by & filed under Part 08: AMINO ACIDS, Treatment.

There are no established criteria for the identification of patients with phenylketonuria who are long-term BH4 responsive. Hennermann et al. reported that, based on their cohort of patients, long-term BH4 responsiveness may be predicted already during neonatal period by determining maximum pretreatment phenylalanine and phenylalanine/tyrosine concentrations, neonatal BH4 loading and PAH genotype. The most predictive […]

Combining GWAS & Gaussian graphical modeling with metabolomics to predict the identity of unknown metabolites.

Posted by & filed under Tools.

Genetic variation in the human genome has been recently linked to differences in individual metabolite levels by combining GWAS studies and metabolomic tools. A considerable amount of the molecules currently quantified by modern metabolomics techniques are chemically unidentified. Krumsiek et al. developed a systems-level approach that combines GWAS studies and Gaussian graphical modeling with metabolomics […]

IVF-gene therapy to prevent mitochondrial disease

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Tachibana et al. demonstrated that the nucleus of an affected woman’s egg could be inserted into healthy donor egg cytoplasm by spindle transfer, allowing the birth of healthy offspring. A child born as a result of this technique will be the genetic child of the patient but carry healthy mitochondrial genes from the donor.   […]

Did the neuron evolve twice?

Posted by & filed under Part 28: NEUROGENETICS, _.

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?

Posted by & filed under Part 28: NEUROGENETICS.

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 […]

Genetic engineering treatment with zinc-finger nucleases

Posted by & filed under Treatment.

The most lethal etiologic agent of malaria is the Plasmodium falciparum parasite. Straimer et al. (2012) report on the successful genetic engineering of Plasmodium falciparum using zinc-finger nucleases (ZFNs), as a potential treatment for malaria refractory to existing medication. ZFNs produce a double-strand break in a user-defined locus and trigger homology-directed repair. To realize the […]

Nitisinone (NTBC) in Hepatorenal tyrosinemia

Posted by & filed under Newborn screening, Treatment.

Hepatorenal tyrosinemia (HT1, fumarylacetoacetate hydrolase deficiency), can cause severe hepatic, renal and peripheral nerve damage. The clinical course of 78 patients was studied in Quebec. Of note, in Quebec HT1 is more frequent and is part of the neonatal screening program. Nitisinone (NTBC) inhibits tyrosine degradation prior to the formation of toxic metabolites like succinylacetone […]