Rapid response of a cardiac rhabdomyoma causing severe right ventricular outflow obstruction to Sirolimus in an infant with negative genetics for Tuberous sclerosis.

Mammalian target of rapamycin inhibitors was found recently to be an effective treatment for manifestations of Tuberous sclerosis complex, including cardiac rhabdomyomas. Most cases with Cardiac rhabdomyoma treated with mammalian target of rapamycin inhibitors to date were diagnosed with Tuberous sclerosis. We report a case of cardiac rhabdomyoma and severe right ventricular outflow obstruction in a baby with negative genetics for Tuberous sclerosis that responded rapidly to Sirolimus.

Serum starvation enhances nonsense mutation readthrough.

Of all genetic mutations causing human disease, premature termination codons (PTCs) that result from splicing defaults, insertions, deletions, and point mutations comprise around 30%. From these mutations, around 11% are a substitution of a single nucleotide that change a codon into a premature termination codon. These types of mutations affect several million patients suffering from a large variety of genetic diseases, ranging from relatively common inheritable cancer syndromes to muscular dystrophy or very rare neuro-metabolic disorders. Over the past three decades, genetic and biochemical studies have revealed that certain antibiotics and other synthetic molecules can act as nonsense mutation readthrough-inducing drugs. These compounds bind a specific site on the rRNA and, as a result, the stop codon is misread and an amino acid (that may or may not differ from the wild-type amino acid) is inserted and translation occurs through the premature termination codon. This strategy has great therapeutic potential. Unfortunately, many readthrough agents are toxic and cannot be administered over the extended period usually required for the chronic treatment of genetic diseases. Furthermore, readthrough compounds only restore protein production in very few disease models and the readthrough levels are usually low, typically achieving no more than 5% of normal protein expression. Efforts have been made over the years to overcome these obstacles so that readthrough treatment can become clinically relevant. Here, we present the creation of a stable cell line system that constitutively expresses our dual-reporter vector harboring two cancer initiating nonsense mutations in the adenomatous polyposis coli (APC) gene. This system will be used as an improved screening method for isolation of new nonsense mutation readthrough inducers. Using these cell lines as well as colorectal cancer cell lines, we demonstrate that serum starvation enhances drug-induced readthrough activity, an observation which may prove beneficial in a therapeutic scenario that requires higher levels of the restored protein. KEY MESSAGES: Nonsense mutations affects millions of people worldwide. We have developed a nonsense mutation read-through screening tool. We find that serum starvation enhances antibiotic-induced nonsense mutation read-through. Our results suggest new strategies for enhancing nonsense mutation read-through that may have positive effects on a large number of patients.

Comparing the Performance of Amplatzer® and Occlutech® Figulla® Septal Occluders: The Pediatric Point of View. A Retrospective Study.

BACKGROUND: The closure of an atrial septal defect is procedure that is frequently performed in both adults and children. Currently, the most commonly used devices are the Amplatzer® and Occlutech® Figulla® atrial septal occluders. Studies conducted in adults have shown that these devices all have similar performance efficiency for the closure of secundum atrial septal defects. No study to date has examined their performance in the pediatric population. OBJECTIVES: To evaluate and compare the performance of Amplatzer® and Occlutech® Figulla® atrial septal occluders in the pediatric population. METHODS: A consecutive retrospective study of exclusively pediatric patients who underwent percutaneous closure of atrial septal defect with these devices was conducted at our institute. RESULTS: The study comprised 110 children, 50 in the Amplatzer® device group and 60 in the Occlutech® Figulla® device group. The groups had similar demographic and defect characteristics, except for defect size per transesophageal echocardiography (TEE), which was 2.1 mm larger in the Amplatzer® device group (P = 0.02). No adverse events were recorded in either of the study groups. Complete defect closure at 12 months follow-up (procedural success) was achieved in all but one of the patients in the Amplatzer® group and all but two in the Figulla® group (P = 1). The residual shunt rates of fenestrated defects were similar in the two groups. CONCLUSIONS: For children with an isolated secundum atrial septal defect, percutaneous closure is equally safe and effective with either Amplatzer® or Occlutech® Figulla® devices.