Browsing by Subject "Patent foramen ovale"

Now showing 1 - 4 of 4
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    Characterization of a novel deep-intronic variant in DYNC2H1 identified by whole-exome sequencing in a patient with a lethal form of a short-rib thoracic dysplasia type III
    (Cold Spring Harbor Laboratory, 2022-12-28) Buchh, Muqsit; Gillespie, Patrick J.; Treat, Kayla; Abreu, Marco A.; Schwantes-An, Tae-Hwi Linus; Helm, Benjamin M.; Fang, Fang; Xuei, Xiaoling; Mantcheva, Lili; Suhrie, Kristen R.; Graham, Brett H.; Conboy, Erin; Vetrini, Francesco; Medical and Molecular Genetics, School of Medicine
    Biallelic pathogenic variants in DYNC2H1 are the cause of short-rib thoracic dysplasia type III with or without polydactyly (OMIM #613091), a skeletal ciliopathy characterized by thoracic hypoplasia due to short ribs. In this report, we review the case of a patient who was admitted to the Neonatal Intensive Care Unit (NICU) of Indiana University Health (IUH) for respiratory support after experiencing respiratory distress secondary to a small, narrow chest causing restrictive lung disease. Additional phenotypic features include postaxial polydactyly, short proximal long bones, and ambiguous genitalia were noted. Exome sequencing (ES) revealed a maternally inherited likely pathogenic variant c.10322C > T p.(Leu3448Pro) in the DYNC2H1 gene. However, there was no variant found on the paternal allele. Microarray analysis to detect deletion or duplication in DYNC2H1 was normal. Therefore, there was insufficient evidence to establish a molecular diagnosis. To further explore the data and perform additional investigations, the patient was subsequently enrolled in the Undiagnosed Rare Disease Clinic (URDC) at Indiana University School of Medicine (IUSM). The investigators at the URDC performed a reanalysis of the ES raw data, which revealed a paternally inherited DYNC2H1 deep-intronic variant c.10606-14A > G predicted to create a strong cryptic acceptor splice site. Additionally, the RNA sequencing of fibroblasts demonstrated partial intron retention predicted to cause a premature stop codon and nonsense-mediated mRNA decay (NMD). Droplet digital RT-PCR (RT-ddPCR) showed a drastic reduction by 74% of DYNCH2H1 mRNA levels. As a result, the intronic variant was subsequently reclassified as likely pathogenic resulting in a definitive clinical and genetic diagnosis for this patient. Reanalysis of ES and fibroblast mRNA experiments confirmed the pathogenicity of the splicing variants to supplement critical information not revealed in original ES or CMA reports. The NICU and URDC collaboration ended the diagnostic odyssey for this family; furthermore, its importance is emphasized by the possibility of prenatally diagnosing the mother's current pregnancy.
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    National Trends, In-Hospital Mortality, and Outcomes of Atrial Septal Defect/Patent Foramen Ovale Closure Procedure: An Analysis From the National Inpatient Sample
    (Elsevier, 2024-05-22) Patel, Kunal N.; Majmundar, Vidit; Majmundar, Monil; Zala, Harshvardhan; Doshi, Rajkumar; Patel, Vyoma; Dani, Sourbha S.; Zeb, Irfan; Patel, Brijesh; Kalra, Ankur; Medicine, School of Medicine
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    Outcomes of Patent Foramen Ovale Transcatheter Closure: Should a Short Aortic Rim Preclude Closure?
    (Elsevier, 2023-03-22) Stefanescu Schmidt, Ada C.; Abrahamyan, Lusine; Muthuppalaniappan, Annamalar; Gorocica Romero, Ricardo; Ephrem, Georges; Everett, Karl; Lee, Douglas S.; Osten, Mark; Benson, Leland N.; Horlick, Eric M.; Medicine, School of Medicine
    Background: The risk of erosion of an atrial septal closure device, in particular the Amplatzer Septal Occluder, has been described as higher in patients with a short aortic rim. Similar concern has been applied to patent foramen ovale (PFO) closure devices, but there are only rare reported cases of erosion. It may be that smaller devices are chosen due to fear of device erosion in PFO patients when this is not necessarily an issue. Objectives: The authors aimed to assess outcomes after PFO closure with the Amplatzer PFO device in patients with a short (<9 mm) aortic rim. Methods: We performed a retrospective analysis of PFO closure for any indication, between 2006 and 2017 at a quaternary center. Preprocedural transesophageal echocardiographic parameters including the aortic rim were remeasured. Long-term outcomes were obtained by linkage to provincial administrative databases. Results: Over the study period, 324 patients underwent PFO closure with the Amplatzer PFO device, with a mean age of 49.8 years; 61% had a short aortic rim (<9 mm). The most common indication was cryptogenic stroke (72%); those with longer aortic distance were more likely to have a non-stroke indication for closure, diabetes (15% vs 6.5%, P = 0.04), and heart failure (15.7% vs 4%, P < 0.001). Over a median 7 years of follow-up, there were no cases of device erosion or embolization requiring cardiac surgery. Conclusions: In a large cohort with long-term administrative follow-up (1,394 patient-years), implantation of an Amplatzer PFO device was performed safely even in patients with a short aortic rim.
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    Right Ventricular Infarction Presenting With Refractory Hypoxia Due to Shunting Across a Patent Foramen Ovale
    (Elsevier, 2021-03-03) Wilson, Stephanie M.; Phookan, Sujoy; Kovacs, Richard J.; Medicine, School of Medicine
    Right ventricular infarction is often associated with significant morbidity and mortality. Here, we report a case of right ventricular infarction associated with persistent hypoxia due to acute right-to-left shunting through a patent foramen ovale.