ABSTRACT
Biallelic loss-of-function variants in the thrombospondin-type laminin G domain and epilepsy-associated repeats (TSPEAR) gene have recently been associated with ectodermal dysplasia and hearing loss. The first reports describing a TSPEAR disease association identified this gene is a cause of nonsyndromic hearing loss, but subsequent reports involving additional affected families have questioned this evidence and suggested a stronger association with ectodermal dysplasia. To clarify genotype-phenotype associations for TSPEAR variants, we characterized 13 individuals with biallelic TSPEAR variants. Individuals underwent either exome sequencing or panel-based genetic testing. Nearly all of these newly reported individuals (11/13) have phenotypes that include tooth agenesis or ectodermal dysplasia, while three newly reported individuals have hearing loss. Of the individuals displaying hearing loss, all have additional variants in other hearing-loss-associated genes, specifically TMPRSS3, GJB2, and GJB6, that present competing candidates for their hearing loss phenotype. When presented alongside previous reports, the overall evidence supports the association of TSPEAR variants with ectodermal dysplasia and tooth agenesis features but creates significant doubt as to whether TSPEAR variants are a monogenic cause of hearing loss. Further functional evidence is needed to evaluate this phenotypic association.
Subject(s)
Anodontia/diagnosis , Anodontia/genetics , Ectodermal Dysplasia/diagnosis , Ectodermal Dysplasia/genetics , Genetic Variation , Phenotype , Proteins/genetics , Alleles , Amino Acid Substitution , Cohort Studies , Female , Genetic Association Studies , Genetic Loci , Humans , Male , Mutation , Pedigree , RadiographySubject(s)
Artificial Intelligence/trends , Radiographic Image Interpretation, Computer-Assisted , Radiology/trends , Artificial Intelligence/history , History, 19th Century , History, 20th Century , History, 21st Century , Patient Acceptance of Health Care/statistics & numerical data , Radiology/history , Radiology/methods , Radiology/statistics & numerical data , SoftwareSubject(s)
Genetic Therapy/methods , Immunotherapy, Adoptive/methods , Leukemia, B-Cell/therapy , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/transplantation , Clinical Trials as Topic , Genetic Therapy/history , Genetic Therapy/legislation & jurisprudence , History, 20th Century , History, 21st Century , Humans , Immunotherapy, Adoptive/history , Immunotherapy, Adoptive/legislation & jurisprudence , Leukemia, B-Cell/genetics , Leukemia, B-Cell/immunology , Receptors, Chimeric Antigen/genetics , T-Lymphocytes/immunology , United States , United States Food and Drug AdministrationABSTRACT
A 53 year-old male presented with a one-day history of a swollen arm and dull, aching pain in the right upper extremity. The patient reported commencing exercising daily over the prior week with a modified, oscillating dumbbell; commonly referred to as a Shake Weight. Imaging revealed an occlusive thrombus in the right axillary, proximal brachial and basilic veins. The patient was treated with a 24-hour tPA infusion followed by mechanical thrombectomy, balloon angioplasty, and stent placement for a residual thrombus and stenosis. The patient was discharged the following day on warfarin and aspirin. This is the first report of effort-induced thrombosis of the upper extremity following the use of a modified, oscillating dumbbell. Due to the growing popularity of modified dumbbells and the possible risk for axillary vein thrombosis, consideration should be made to caution consumers of this potential complication.
Subject(s)
Axillary Vein , Exercise Test/instrumentation , Exercise , Sports , Venous Thrombosis/etiology , Humans , Male , Middle Aged , Phlebography , Thrombectomy , Venous Thrombosis/diagnosis , Venous Thrombosis/surgeryABSTRACT
A 23 year old woman presented with sudden onset retrosternal chest pain following an attempt to move a heavy object from her vehicle. Multiple fractured struts of an inferior vena cava filter were identified in the distal right and left pulmonary artery branches, and in the free wall of the right ventricle. A small pericardial effusion was noted. Because of the depth of penetration into the right ventricle, it was perceived not to be amenable to endovascular retrieval. Over several days of observation, she continued to have progressive retrosternal and left shoulder pain. She underwent exploratory sternotomy and extraction of a strut that was partially protruding from the right ventricle and abrading the diaphragmatic pericardium. The patient recovered quite well and was discharged on the third postoperative day.
