A novel causative functional mutation in GATA6 gene is responsible for familial dilated cardiomyopathy as supported by in silico functional analysis.

Dilated cardiomyopathy (DCM), one of the most common types of cardiomyopathies has a heterogeneous nature and can be seen in Mendelian forms. Next Generation Sequencing is a powerful tool for identifying novel variants in monogenic disorders. We used whole-exome sequencing (WES) and Sanger sequencing techniques to identify the causative mutation of DCM in an Iranian pedigree. We found a novel variant in the GATA6 gene, leading to substituting Histidine by Tyrosine at position 329, observed in all affected family members in the pedigree, whereas it was not established in any of the unaffected ones. We hypothesized that the H329Y mutation may be causative for the familial pattern of DCM in this family. The predicted models of GATA6 and H329Y showed the high quality according to PROCHECK and ERRAT. Nonetheless, simulation results revealed that the protein stability decreased after mutation, while the flexibility may have been increased. Hence, the mutation led to the increased compactness of GATA6. Overall, these data indicated that the mutation could affect the protein structure, which may be related to the functional impairment of GATA6 upon H329Y mutation, likewise their involvement in pathologies. Further functional investigations would help elucidating the exact mechanism.

Cardiac Tamponade: A Rare Manifestation of Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) typically presents with recurrent attacks of fever and serosal inflammation with peritoneum, pleura, and synovium. We usually do not expect pericardial involvement at the early stages. FMF is an autoinflammatory disease, usually inherited with an autosomal recessive pattern. The patients typically have biallelic mutations in the MEFV gene, located on chromosome 16. Colchicine is the first-line treatment of FMF, which not only plays a crucial prophylactic role regarding the attack episodes, but also prevents amyloidosis. Colchicine resistance and intolerance in FMF patients have been rarely reported. Alternative anti-inflammatory agents are understood to be helpful in such cases. We describe a 13-year-old boy referred to our pediatric department complaining of chest pain, dyspnea, and tachycardia. Due to the massive pericardial and pleural effusion, a pericardiocentesis was performed, and a chest tube was inserted. Cardiac tamponade was considered as the initial diagnosis. After a month, he faced another episode of pleuritic chest pain, fever, tachycardia, and pleural and pericardial effusion. Evaluation for probable differential diagnoses including infection, malignancy, and collagen vascular disease showed no remarkable results. Finally, the mutation found by whole exome sequencing was confirmed by direct Sanger sequencing revealing a heterozygote c.44G > C (p.Glu148Gln) mutation in exon 2, confirming the clinical diagnosis of familial Mediterranean fever. Since he seemed to be nonresponsive to the maximum standard dose of colchicine, 100 mg of daily dapsone was added to his treatment regimen, which controlled the attack episodes well. FMF, while rarely initiated with cardiac manifestation, should be considered in patients with any early signs and symptoms of cardiovascular involvement.