Posts By: Yannis Trakadis

Cell programming?

Posted by & filed under Part 03: GENERAL THEMES, Tools.

Cells respond to the environment and perform their different functions via computational operations performed by DNA-encoded circuits that process sensory information. More specifically, these operations are performed by networks of regulatory proteins that integrate signals and control the timing of gene expression. Cells can be programmed using synthetic genetic circuits to generate a desired operation. […]

HSCT and genetic conditions

Posted by & filed under Treatment.

Hematopoietic stem cell transplantation (HSCT) with matched unrelated donors can be used in different non-malignant genetic diseases. Abdel-Azim et al. report the outcomes of 15 patients with non-malignant genetic diseases who received HSCT from 2006 to 2014. Fifteen patients were enrolled during the study period: 26.7% female (n = 4), 33.3% Hispanic (n = 5), […]

Hypoxia as a therapy for mitochondrial disease

Posted by & filed under Part 10: DISORDERS OF MITOCHONDRIAL FUNCTION.

Jain et al. performed a genome-wide, Cas9-mediated screen using the human leukemic suspension cell line, K562, to identify factors that are protective during mitochondrial respiratory chain (RC) inhibition. Hypoxia response, an endogenous program evolved to adapt to limiting oxygen availability, was a very interesting finding. Genetic or small molecule activation of the hypoxia response appears […]

Organic acidurias: impact of age at onset and NBS

Posted by & filed under Newborn screening, Part 09: ORGANIC ACIDS.

The information of 567 patients with organic acidurias (OADs) from the E-IMD registry were analysed using recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. Different OADs were included in this study: methylmalonic (MMA, n=164), propionic (PA, n=144), isovaleric (IVA, n=83), and type 1 glutaric aciduria (GA1, n=176). Of […]

Gene therapy and Primary hyperoxaluria type 1

Posted by & filed under Treatment.

Primary hyperoxaluria type 1 (PH1) is a condition caused by a deficiency of the peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). PH1 is estimated to account for about 1% of pediatric cases of end-stage renal failure and to occur in 1:120,000 live births in Europe. It typically presents with renal colic or asymptomatic gross hematuria before the […]

Somatic mutation in single human brain cells

Posted by & filed under Exome sequencing, Part 03: GENERAL THEMES, Part 28: NEUROGENETICS.

Neurons live for decades in a postmitotic state and their genomes are susceptible to DNA damage. Using genome sequencing for individual human brain cells (postmortem), Lodato et al. have searched for somatic single-nucleotide variants (SNVs) in the human brain. After sequencing 36 neurons from the cerebral cortex of three normal individuals, they demonstrated that the […]

Phase 3 Trial in Lysosomal Acid Lipase Deficiency

Posted by & filed under Part 12: LIPIDS, Treatment.

  Lysosomal  acid lipase deficiency can cause cirrhosis and severe dyslipidemia. Burton et al. recently published in N Engl J Med a multicenter, randomized, double-blind, placebo-controlled study involving 66 patients with lysosomal acid lipase deficiency. This was a phase 3 clinical trial of enzyme-replacement therapy in children and adults, using sebelipase alfa. Sebelipase alfa was administered intravenously (1 […]

Meta-analysis: heritability of different traits

Posted by & filed under Part 03: GENERAL THEMES.

Polderman et al. recently published in Nature Genetics a meta-analysis of twin correlations and reported variance components for 17,804 traits. In total, 2,748 publications including 14,558,903 partly dependent twin pairs, virtually all published twin studies of complex traits, were taken into consideration. For 69% of the traits studied, the observed twin correlations are consistent with […]

SAM in creatine transporter deficiency

Posted by & filed under Treatment.

Jaggumantri et al. recently published an open-label observational study to evaluate the effect of adjunct S-adenosyl methionine (SAM) in Creatine transporter (SLC6A8) deficiency. This X-linked condition is characterized by cerebral creatine deficiency, behavioral problems, seizures, hypotonia, and intellectual disability. Only some patients respond to high-dose oral creatine, glycine, and L-arginine supplementation. SAM (50/mg/kg) was used […]

Is BRIEF sufficient to monitor executive function in PKU?

Posted by & filed under Part 08: AMINO ACIDS.

Liemburg et al. (2015) explored if the Behavior Rating Inventory of Executive Function (BRIEF) instrument is sufficient to monitor for Executive Function (EF) deficits in patients with PKU. 55 adult PKU patients (mean age 28.3 ± 6.2 years) filled out the BRIEF-A questionnaire and performed computerized tasks measuring executive functions (inhibition, cognitive flexibility, and working […]