Posts Categorized: _



Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism.

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

Pougovkina O et al. Aberrant protein acylation is a common observation in inborn errors of acyl-CoA metabolism. J Inherit Metab Dis. 2014 Feb 15. [Epub ahead of print]   An elegant study that formulates a new hypothesis for the role of aberrant acyl-CoA accumulation in disorders of acyl-CoA metabolism. Lysine acylation (in particular, acetylation) has […]



Mutation in DMD as a cause of non-specific X-linked intellectual disability without overt muscular dystrophy

Posted by & filed under Part 25: MUSCLE, Part 28: NEUROGENETICS, _.

de Brouwer et al. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy. European Journal of Human Genetics (2014) 22, 480–485.   A very interesting observation, underlining the importance of dystrophin isoforms for the understanding of genotype-phenotype correlations in DMD-associated disorders. The authors describe a family with non-specific X-linked intellectual disability and no clinically observable […]



RNAi therapy in Transthyretin amyloidosis

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Transthyretin amyloidosis is caused by the deposition of transthyretin amyloid in peripheral nerves and the heart. RNA interference (RNAi) targeting messenger RNA transcribed from a disease-causing gene could theoretically be used in the management of the disease by reducing the production of transthyretin. Coelho et al. identified a potent antitransthyretin small interfering RNA, which was […]



Yersinia pestis and the Plague of Justinian 541–543 AD: a genomic analysis

Posted by & filed under Historical perspectives, _.

Wagner DM et al. Yersinia pestis and the Plague of Justinian 541-543 AD: a genomic analysis. Lancet Infect Dis. 2014 Jan 27. pii: S1473-3099(13)70323-2. doi: 10.1016/S1473-3099(13)70323-2. [Epub ahead of print] In a fascinating study, Wagner et al explore the nature of the first plague pandemic (the Plague of Justinian, 6-8th centuries), and in particular its genetic relationship to the second and third pandemics (respectively, the Black death […]



VPS53 mutations cause progressive cerebello-cerebral atrophy type 2

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

Feinstein M et al. VPS53 mutations cause progressive cerebello-cerebral atrophy type 2. J Med Genet. 2014 Feb 27. doi: 10.1136/jmedgenet-2013-101823. [Epub ahead of print] Progressive cerebello-cerebral atrophy (PCCA), first described in 2003 in six Sephardi Jewish families, is a devastating autosomal recessive neurodegenerative condition presenting in childhood with psychomotor regression, acquired microcephaly, spastic quadriplegia and epilepsy. Neuroimaging […]



Repeat sequences in the genomic DNA of the TAZ gene

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

Barth syndrome, a disorder of dilated cardiomyopathy and neutropenia, is caused by mutations in TAZ on chromosome Xq28. Analysis of the genomic sequence of this gene has revealed that about 45% of the sequence is composed of SINES and LINES and three quarters of these interspersed repeat sequences are Alu sequences. Ferri et al. (Orphanet J Rare Dis, 2013, 8(1): 27) […]



Adjunct treatments for LSD therapy

Posted by & filed under Part 16: LYSOSOMAL DISORDERS, _.

Enzyme replacement therapy and substrate reduction therapy  have had an incredible impact on the treatment of many lysosomal storage disorders (LSDs). However, in some LSDs the disorder continues to progress, in part due to downstream pathologic processes instigated by the storage material. Williams et al. Neurobiol Dis (2014) March (Epub) report that combination therapy  with miglustat, curcumin and ibuprofen provide […]



Newborn screening cards and tranport concerns

Posted by & filed under Newborn screening, _.

The effects of environmental temperature on newborn screening results for galactosemia are well known amongst biochemical geneticists. However, environmental effects on many other aspects of the newborn screen are not commonly known. Golbahar et al (J Med Screen, 2014, Feb) studied the effect of heat and humidity on acylcarnitines and amino acids on dried blood spots […]



De novo mutations in schizophrenia implicate synaptic networks.

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It is known that the genetic risk for schizophrenia is mostly accounted for by inherited alleles. However, recently, de novo mutations (large chromosomal copy number changes) have been shown to occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Fromer et al. demonstrated that small de novo mutations, affecting one […]



A polygenic burden of rare disruptive mutations in schizophrenia.

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Purcell et al. analysed the exome sequences of 2,536 schizophrenia cases and 2,543 controls and identified a polygenic burden primarily arising from rare, disruptive mutations distributed across many genes. The genes encoding voltage-gated calcium ion channel and the signalling complex formed by the ARC protein of the postsynaptic density were particularly enriched. A polygenic burden […]