Publications by authors named "Sara Markholt"

5 Publications

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Delineation of musculocontractural Ehlers-Danlos Syndrome caused by dermatan sulfate epimerase deficiency.

Mol Genet Genomic Med 2020 05 4;8(5):e1197. Epub 2020 Mar 4.

Center for Medical Genetics, Shinshu University Hospital, Matsumoto, Japan.

Background: Musculocontractural Ehlers-Danlos Syndrome (mcEDS) is a rare connective tissue disorder caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE (mcEDS-DSE), both of which result in defective dermatan sulfate biosynthesis. Forty-one patients with mcEDS-CHST14 and three patients with mcEDS-DSE have been described in the literature.

Methods: Clinical, molecular, and glycobiological findings in three additional patients with mcEDS-DSE were investigated.

Results: Three patients from two families shared craniofacial characteristics (hypertelorism, blue sclera, midfacial hypoplasia), skeletal features (pectus and spinal deformities, characteristic finger shapes, progressive talipes deformities), skin features (fine or acrogeria-like palmar creases), and ocular refractive errors. Homozygous pathogenic variants in DSE were found: c.960T>A/p.Tyr320* in patient 1 and c.996dupT/p.Val333Cysfs*4 in patients 2 and 3. No dermatan sulfate was detected in the urine sample from patient 1, suggesting a complete depletion of DS.

Conclusion: McEDS-DSE is a congenital multisystem disorder with progressive symptoms involving craniofacial, skeletal, cutaneous, and cardiovascular systems, similar to the symptoms of mcEDS-CHST14. However, the burden of symptoms seems lower in patients with mcEDS-DSE.
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http://dx.doi.org/10.1002/mgg3.1197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216804PMC
May 2020

A case of penta X syndrome caused by nondisjunction in maternal meiosis 1 and 2.

Clin Case Rep 2017 07 1;5(7):1136-1140. Epub 2017 Jun 1.

Department of Clinical Genetics Aarhus University Hospital Aarhus Denmark.

The prenatal abnormalities in patients with penta X syndrome appear late in pregnancy and are nonspecific. In contrast, the postnatal phenotype is well described although new findings are still revealed. Penta X syndrome is a result of successive nondisjunctions of the X chromosomes in both maternal meiotic divisions.
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http://dx.doi.org/10.1002/ccr3.1004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494398PMC
July 2017

Toxicological aspects of injectable gold-hyaluronan combination as a treatment for neuroinflammation.

Histol Histopathol 2014 Apr 11;29(4):447-56. Epub 2013 Oct 11.

Department of Biomedicine - Pharmacology, Aarhus University, Denmark.

Secondary inflammatory reactions to stroke or trauma contribute to irreplaceable loss of brain tissue of the affected patients. Likewise, neuroinflammatory processes are the main pathophysiological feature in Multiple Sclerosis (MS), a common neurodegenerative disease among young adults. In the search for safe and efficient ways to reduce inflammation within nervous tissue older immunosuppressive remedies have been re-investigated. The anti-inflammatory properties of gold salts are well known but result in uncontrollable systemic spread of gold ions, generating side effects such as nephrotoxicity, limiting their use. Recent studies have circumvented this obstacle by introducing metallic gold implants as a localized source of immune-modulating gold ions and suspension in hyaluronic acid (HA) enables injection of small amounts of gold in the natural spaces of the brain. By injecting >25 μm gold beads in HA intracerebrally we recently showed a slowing of disease progression in a rodent model of MS. The toxicological aspects were, however, not assessed. The present study investigates the viability of neuronal and macrophage cell cultures exposed to the gold/HA combination and the possible risk associated with unilateral gold/HA injection in young Balb/CA mice in the first 7 to 21 days of gold-exposure. Tracing by autometallography of gold accumulations throughout the brain exhibited sparse gold uptake in glia and neurons of hippocampus and cortex, and striatum and cerebellum were void of staining. No systemic spread of gold was seen in liver or kidney, nor were there signs of obstruction of the ventricular system. Both cell cultures of J774 macrophages and CCL neurons accumulated gold from gold/HA-exposure with no signs of reduced viability. In conclusion, our findings indicate that gold/HA is not overtly neuro- or cytotoxic, nor does intraventricular exposure result in widespread gold accumulation or tissue damage, warranting further studies into the pharmacological properties of this novel form of gold treatment.
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http://dx.doi.org/10.14670/HH-29.10.447DOI Listing
April 2014

Metallic silver fragments cause massive tissue loss in the mouse brain.

Basic Clin Pharmacol Toxicol 2011 Jul 9;109(1):1-10. Epub 2011 Feb 9.

Section of Neurobiology, Department of Anatomy, Aarhus University, Aarhus, Denmark.

Silver is a metal with well-known antibacterial effects. This makes silver an attractive coating material for medical devices for use inside the body, e.g. orthopaedic prostheses and catheters used in neurosurgery as it has been found to reduce the high risk of infections. Lately, the use of nano-silver particles in the industry, e.g. woven into fabrics and furniture has increased, and thus the exposure to silver particles in daily life increases. To study the effect of metallic silver particles on nervous tissue, we injected micron-sized silver particles into the mouse brain by stereotactic procedures. After 7, 14 days and 9 months, the silver-exposed animals had considerable brain damage seen as cavity formation and inflammation adjacent to the injected metallic silver particles. The tissue loss involved both cortical and hippocampal structures and resulted in enlargement of the lateral ventricles. Autometallographic silver enhancement showed silver uptake in lysosomes of glia cells and neurons in the ipsilateral cortex and hippocampus alongside a minor uptake on the contralateral side. Silver was also detected in ependymal cells and the choroid plexus. After 9 months, spreading of silver to the kidneys was seen. Cell counts of immunostained sections showed that metallic silver induced a statistically significant inflammatory response, i.e. increased microgliosis (7 days: p < 0.0001; 14 days: p < 0.01; 9 months: p < 0.0001) and TNF-α expression (7 and 14 days: p < 0.0001; 9 months: p = 0.91). Significant astrogliosis (7, 14 days and 9 months: p < 0.0001) and increased metallothionein (MT I + II) expression (7 and 14 days: p < 0.0001; 9 months: p < 0.001) were also seen in silver-exposed brain tissue. We conclude that metallic silver implants release silver ions causing neuroinflammation and a progressive tissue loss in the brain.
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http://dx.doi.org/10.1111/j.1742-7843.2010.00668.xDOI Listing
July 2011

Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue.

Acta Obstet Gynecol Scand 2010 Dec 5;89(12):1589-91. Epub 2010 Nov 5.

Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, Copenhagen University Hospital, Copenhagen University, Denmark.

Cryopreservation of ovarian tissue is a promising new technique for fertility preservation in patients facing gonadotoxic treatment. Ovarian tissue is extracted and cryo-stored at low temperature prior to treatment. If the woman becomes menopausal, the tissue can be transplanted and a few months later the woman will start to ovulate and be able to conceive, naturally or with assisted reproduction treatment. Currently, 12 healthy children have been born worldwide as a result of transplanting frozen/thawed ovarian tissue. Of these children 3 are Danish and a number of other Danish women are currently attempting to become pregnant. One of these women conceived naturally and had a normal intrauterine pregnancy following transplantation of cryopreserved ovarian tissue. However, the woman decided to terminate the pregnancy within the legal time frame. This pregnancy imposes cryopreservation of ovarian tissue for fertility preservation as a valid method and illustrates that personal life circumstances may rapidly change.
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http://dx.doi.org/10.3109/00016349.2010.512074DOI Listing
December 2010