RESUMEN
Pediatric cardiomyopathies are mostly attributed to variants in sarcomere-related genes. Unfortunately, the genetic architecture of pediatric cardiomyopathies has never been previously studied in Jordan. We sought to uncover the genetic landscape of 14 patients from nine families with several subtypes of pediatric cardiomyopathies in Jordan using Exome sequencing (ES). Our investigation identified pathogenic and likely pathogenic variants in seven out of nine families (77.8%), clustering in sarcomere-related genes. Surprisingly, phenocopies of sarcomere-related hypertrophic cardiomyopathies were evident in probands with glycogen storage disorder and mitochondrial-related disease. Our study underscored the significance of streamlining ES or expanding cardiomyopathy-related gene panels to identify plausible phenocopies of sarcomere-related cardiomyopathies. Our findings also pointed out the need for genetic testing in patients with cardiomyopathy and their at-risk family members. This can potentially lead to better management strategies, enabling early interventions, and ultimately enhancing their prognosis. Finally, our findings provide an initial contribution to the currently absent knowledge about the molecular underpinnings of cardiomyopathies in Jordan.
Asunto(s)
Cardiomiopatías , Linaje , Sarcómeros , Humanos , Jordania , Masculino , Femenino , Sarcómeros/genética , Niño , Cardiomiopatías/genética , Cardiomiopatías/diagnóstico , Preescolar , Secuenciación del Exoma , Lactante , Fenotipo , Adolescente , Mutación , Pruebas Genéticas/métodosRESUMEN
Brachial artery pseudoaneurysms (PSA) are considered uncommon, but they can be limb and life threatening. Most etiologies are related to iatrogenic injury or following a fracture. Here we present a 37-year-old male complaining of a large swelling in his right upper arm that was gradually increasing in size for the last 7 months. It started with a sudden onset of pain while lifting heavy boxes at his daily job. Ultrasound and MRA showed a pseudoaneurysm of the right brachial artery. Resection of the PSA was performed with a vein interposition graft. This case illustrates the significance of considering PSA as a differential diagnosis in patients presenting with upper arm swelling without history of obvious trauma.
RESUMEN
Variants in Tbox transcription factor 5 (TBX5) can result in a wide phenotypic spectrum, specifically in the heart and the limbs. TBX5 has been implicated in causing nonsyndromic cardiac defects and HoltOram syndrome (HOS). The present study investigated the underlying molecular etiology of a family with heterogeneous heart defects. The proband had mixedtype total anomalous pulmonary venous return (mixedtype TAPVR), whereas her mother had an atrial septal defect. Genetic testing through triobased wholeexome sequencing was used to reveal the molecular etiology. A nonsense variant was identified in TBX5 (c.577G>T; p.Gly193*) initially showing cosegregation with a presumably nonsyndromic presentation of congenital heart disease. Subsequent genetic investigations and more complete phenotyping led to the correct diagnosis of HOS, documenting the novel association of mixedtype TAPVR with HOS. Finally, protein modeling of the mutant TBX5 protein that harbored this pathogenic nonsense variant (p.Gly193*) revealed a substantial drop in the quantity of noncovalent bonds. The decrease in the number of noncovalent bonds suggested that the resultant mutant dimer was less stable compared with the wildtype protein, consequently affecting the protein's ability to bind DNA. The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixedtype TAPVR with TBX5. Prior to the current analysis, the molecular association of TAPVR with HOS had never been documented; hence, this is the first genetic investigation to report the association between TAPVR and HOS. Furthermore, it was demonstrated that the nullvariants reported in the Tbox domain of TBX5 were associated with a wide range of cardiac and/or skeletal anomalies on both the interand intrafamilial levels. In conclusion, genetic testing was highlighted as a potentially powerful approach in the prognostication of the proper diagnosis.