Exome Sequencing Identifies a Novel FBN1 Variant in a Pakistani Family with Marfan Syndrome That Includes Left Ventricle Diastolic Dysfunction.

INTRODUCTION: Cardiomyopathies are diseases of the heart muscle and are important causes of heart failure. Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy that can be acquired, syndromic or non-syndromic. The current study was conducted to explore the genetic defects in a Pakistani family with cardiac disease and features of Marfan's syndrome (MFS). METHODS: A family with left ventricle (LV) diastolic dysfunction and MFS phenotype was assessed in Pakistan. The clinical information and blood samples from the patients were collected after physical, cardiovascular, and ophthalmologic examinations. An affected individual (proband) was subjected to whole-exome sequencing (WES). The findings were further validated through Sanger sequencing in the family. RESULTS: Through WES and sanger validation, we identified a novel variant NM_000138.4; c.1402A>G in the Fibrillin-1 (FBN1) gene that segregates with LV diastolic dysfunction and MFS. Furthermore, bioinformatic evaluation suggested that the novel variant is deleterious and disease-causing. CONCLUSIONS: This study identified for the first time a novel FBN1 variant in a family with LV diastolic dysfunction and MFS in Pakistan.

Computed tomography findings in cerebral hydatid disease.

AIM: To describe imaging findings of cerebral hydatid cysts on computed tomography of brain. MATERIAL AND METHODS: We retrospectively reviewed CT scans of brain in 5 patients with pathologically confirmed hydatid cysts in cerebral hemispheres. The patients were scanned either on a spiral (single slice) CT or on multidetector-row CT before and after intravenous injection of iodinated contrast material. RESULTS: All the patients were children aged 8 to 13 years with 3 boys and 2 girls. Features of raised intracranial tension were present in all the cases at presentation. CT findings of a large intracerebral cystic lesion with significant mass effect and without any calcification or enhancement were common in all 5 cases. Perilesional edema was present in 1 case. Cerebral hydatid was seen as either a homogenous fluid attenuation unilocular cyst (3 cases) or a unilocular cyst with few peripheral daughter cysts (1 case) or cyst filled by multiple daughter cysts inside (1 case). All the cases were operated and cyst was removed completely after craniotomy. CONCLUSION: Accurate preoperative diagnosis of cerebral hydatid by CT followed by surgery with care to avoid cyst rupture can result in favorable outcome.