Posts By: Hilary Vernon

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 […]

Mutations in CoA Synthase as a cause of NBIA

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

Dusi et al (AJHG, 94, 11-22) report mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation (NBIA). This gene is particularly interesting, as another member of the CoA biosynthetic pathway, PANK2, also causes NBIA. It is not clear why a gene with such seemingly ubiquitous function should cause such specific neurologic […]

Mutations in PTDSS1 cause Lenz-Majewski Syndrome

Posted by & filed under New IEM.

Sousa et al. (Nature genetics, volume 46 (1) 2013: 70-76) recently reported that mutations in PTDSS1 cause Lenz-Majewski Syndrome (LMS). This discovery was made via whole exome sequencing on 4 affected patients. The mutations are gain of function mutations that impair negative feedback regulation of the end product, phosphatidylserine, Interestingly, while synthesis of phosphatidylserine is […]


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

I have been seeing a patient for several  years who carried a clinical diagnosis of a mitochondrial disorder based on chronic lactic acidosis, brain abnormalities and other organ involvement. However,  a molecular diagnosis was elusive despite mtDNA sequencing and various gene panels. I therefore recently sent whole exome sequencing on this patient, and he was […]

Mitochondrial disease and Sideroflexin 4

Posted by & filed under Exome sequencing.

Hildick-Smith et al (AJHG, 2013, 5(93) 906-914) used whole exome sequencing in two probands with mitochondrial disease to identify SFXN4 as a candidate gene for the etiology of their disorder. They then were able to take advantage of fibroblast complementation assays  and a zebrafish knockdown model to validate SFXN4 as the causative gene. With increasing utilization of whole exome sequencing […]

toxicity of 3-hydroxylated fatty acids

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Cardiomyopathy is a well known complication of LCHAD deficiency and Mitochondrial Trifunctional protein (MTP) deficiency. Tonin et al (in J Bioenerg Biomech 2013 Feb;45(1-2):47-57) offer evidence that several 3-hydroxylated fatty acids that accumulate in MTP and LCHAD deficiencies act as uncouplers of oxidative phosphorylation.This could potentially interfere with cardiac energy homeostasis. It would be interesting to better understand […]

Glycerol phenylbutyrate and hepatic encephalopathy

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Our genetics service has been consulted several times recently about whether or not nitrogen scavenging agents typically used in urea cycle disorders would be useful in individuals with hepatic encephalopathy (HE) due to liver failure, i.e. from cirrhosis. Our a priori reasoning was that these scavenging agents may not be as effective in HE because they rely on alternative […]

Mitochondrial Cristae and Supercomplexes

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In a very well thought out group of experiments, Cogliati et al. demonstrated the effect that disturbed mitochondrial cristae shape has on respiratory chain supercomplexes (Cell, 155, (2013)160-171). This supercomplex effect has implications for cell growth, apoptosis, and respiratory efficiency. These studies suggest potentially interesting pathophysiological mechanisms for other disorders affecting cristae organization, such as 3-methyglutaconic […]