Identification of the first homozygous 1-bp deletion in GDF9 gene leading to primary ovarian insufficiency by using targeted massively parallel sequencing.

Targeted massively parallel sequencing (TMPS) has been used in genetic diagnosis for Mendelian disorders. In the past few years, the TMPS has identified new and already described genes associated with primary ovarian insufficiency (POI) phenotype. Here, we performed a targeted gene sequencing to find a genetic diagnosis in idiopathic cases of Brazilian POI cohort. A custom SureSelectXT DNA target enrichment panel was designed and the sequencing was performed on Illumina NextSeq sequencer. We identified 1 homozygous 1-bp deletion variant (c.783delC) in the GDF9 gene in 1 patient with POI. The variant was confirmed and segregated using Sanger sequencing. The c.783delC GDF9 variant changed an amino acid creating a premature termination codon (p.Ser262Hisfs*2). This variant was not present in all public databases (ExAC/gnomAD, NHLBI/EVS and 1000Genomes). Moreover, it was absent in 400 alleles from fertile Brazilian women screened by Sanger sequencing. The patient's mother and her unaffected sister carried the c.783delC variant in a heterozygous state, as expected for an autosomal recessive inheritance. Here, the TMPS identified the first homozygous 1-bp deletion variant in GDF9. This finding reveals a novel inheritance pattern of pathogenic variant in GDF9 associated with POI, thus improving the genetic diagnosis of this disorder.

Evaluation of bone mineral density and microarchitectural parameters by DXA and HR-pQCT in 37 children and adults with X-linked hypophosphatemic rickets.

In X-linked hypophosphatemic (XLH) rickets, dual-energy X-ray absorptiometry (DXA) measurements must be analyzed with caution. High-resolution peripheral quantitative computed tomography (HR-pQCT) analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex. INTRODUCTION: The purpose of this study is to evaluate bone mineral density (BMD) and microarchitecture in 37 patients (13 children and 24 adults) with XLH confirmed by PHEX mutations from a tertiary center compared to healthy controls. METHODS: Areal BMD (aBMD) was evaluated by DXA, whereas volumetric BMD (vBMD) and microarchitectural parameters were analyzed by HR-pQCT. RESULTS: Adult XLH patients had higher lumbar aBMD (p < 0.01) than the controls. At the radius, the vBMD was similar between XLH patients and controls. At the tibia, XLH patients had lower total vBMD (p = 0.04), likely resulting from decreased trabecular vBMD (p < 0.01), and this difference was observed in the children and adult groups. Analysis based on metabolic status showed that the adult XLH patients with non-compensated disease had lower cortical vBMD at the tibia than the compensated XLH patients (p = 0.03). The microarchitectural differences at the radius and tibia included lower trabecular number (p < 0.01), greater trabecular separation (p < 0.01), and higher trabecular network inhomogeneity (p < 0.01) in XLH patients compared to their controls. At the radius, adults exhibited greater trabecular deficits than were seen in children. CONCLUSIONS: In XLH patients, DXA measurements must be analyzed with caution due to the interference of anatomic and anthropometric factors. HR-pQCT analysis suggested that XLH primarily affects the cancellous compartment, with the tibia more affected than the radius. Effective treatment of XLH appears to positively affect bone mineralization, mainly in the bone cortex.

Petersen's hernia as a complication of bariatric surgery: CT findings.

Referrals for bariatric surgery have currently increased due to the need for more effective interventions in the management of severely obese patients. The Roux-en-Y gastric bypass is currently one of the preferred procedures, and internal hernias are the main causes of late postoperative complication. Petersen's hernia is a less common finding in most published papers compared to transmesocolic hernia, however, it seems to be increasing in incidence (in our service, eight cases which have been tomographic diagnosed in 2 years, were confirmed by laparoscopic surgery). The clinical findings are not specific, usually with abdominal pain, associated or not with abdominal distention and vomiting. In this context, imaging exams have an important role in the early diagnosis and surgery of this condition, with multislice computed tomography being the most accurate method. The aim of this pictorial essay is to the demonstrate the main CT findings associated with Petersen's hernia in patients who underwent Roux-en-Y gastric bypass.

The role of gallium-67 scan in defining the extent of disease in an endemic deep mycosis, paracoccidioidomycosis: a predominantly multifocal disease.

The tools currently used to evaluate the extent of paracoccidioidomycosis (PCM) may be of limited value in detecting subclinical lesions. The aim of this study was to verify the role of gallium-67 whole-body scan in evaluating the extent of disease of 65 patients with active PCM. The (67)Ga scan findings were compared with the results of clinical evaluation, chest radiography and/or high-resolution computed tomography (CT), abdominal ultrasound (US) or CT, laryngoscopy, CT or magnetic resonance imaging (MRI) of the head, and technetium-99m methylene diphosphonate bone scan, obtained before treatment. Clinically unsuspected lesions were detected by imaging procedures in 21 patients (32%), mainly in the lungs (n=11), adrenals (n=6), and superficial (n=3) and deep lymph nodes (n=14). (67)Ga scan detected 100% of the cases with subclinical involvement in the lungs. Scintigraphy was superior to chest radiography in demonstrating lung disease (94% vs 81%). The lymphatic lesions were demonstrated by (67)Ga scan in all the clinically suspected cases and in nearly all unsuspected cases, and also revealed more extensive involvement than was clinically suspected in many of them. There was good agreement between (67)Ga scan and the other imaging procedures for the initial detection of thoracic and abdominal lymph nodes and bone involvement. (67)Ga imaging detected most cases of laryngopharyngeal disease with active inflammatory lesions found at indirect laryngoscopy. On the other hand, (67)Ga scan failed to demonstrate most of the adrenal and CNS lesions detected by abdominal US/CT and head CT/MRI. In conclusion, (67)Ga imaging is a useful tool for evaluating the location and extent of suspected and unsuspected lesions in PCM. It could serve as a screening method before the use of other diagnostic procedures, particularly in the detection of lung, superficial and deep lymph node and bone involvement.

Chronic pulmonary paracoccidioidomycosis (South American blastomycosis): high-resolution CT findings in 41 patients.

OBJECTIVE: To assess the pulmonary parenchymal findings on high-resolution CT in 41 patients with the chronic form of paracoccidioidomycosis (South American blastomycosis). SUBJECTS AND METHODS: The study included 41 consecutive patients in whom chronic paracoccidioidomycosis had been proven. All patients underwent high-resolution CT (1-mm collimation, high-spatial-frequency reconstruction algorithm) at 12 equally spaced intervals through the chest. The images were analyzed by two radiologists, and each final decision was reached by consensus. RESULTS: Thirty-eight (93%) of the 41 patients had CT scans with abnormal findings. The findings included interlobular septal thickening in 36 patients (88%), 1-25 mm diameter nodules in 34 (83%), peribronchovascular interstitial thickening in 32 (78%), centrilobular opacities in 26 (63%), intralobular lines in 24 (59%), ground-glass opacities in 14 (34%), cavitation in seven (17%), air-space consolidation in five (12%), traction bronchiectasis in 34 (83%), and paracicatricial emphysema in 28 (68%). In approximately 90% of patients, the abnormalities were bilateral and symmetrical and involved all lung zones. CONCLUSION: High-resolution CT findings of paracoccidioidomycosis consist predominantly of interstitial abnormalities and nodules associated with traction bronchiectasis and paracicatricial emphysema in a bilaterally symmetrical distribution.

Calcification in primary lung non-Hodgkin lymphoma.

Calcification in lymphoma before treatment or after chemotherapy is extremely rare. There have been scarse reports of calcified masses due to Hodgkin and non-Hodgkin lymphomas, originating in the main lymphatic chains of the mediastinum and retroperitoneum. We report a case of primarily extra-nodal (pulmonary) non-Hodgkin lymphoma with calcification prior to current treatment.

MRI and ultrasound detection of asymptomatic thyroid nodules in hyperparathyroidism.

A retrospective MRI and ultrasound (US) study of 50 patients with hyperparathyroidism and no history of thyroid disease was done. The purpose was to compare the sensitivity of both methods in the detection of asymptomatic thyroid nodules, as well as to determine the prevalence of thyroid abnormalities in patients with hyperparathyroidism. All the patients underwent MR and 33 were also studied by high-resolution US. Magnetic resonance imaging was performed on a 1.5 T unit, using T1-(500-700/20) and T2-(2,000/20 and 70) weighted images. Axial sections (5 mm with a 1 mm interval between them) were obtained along the neck. Ultrasonography was performed using a 10 MHz linear array transducer. The prevalence of thyroid nodules was 46% in the 50 patients studied by MR imaging. In the subgroup of patients studied by both methods, US depicted nodules in 48% of patients, and MR depicted nodules in 45%. Magnetic resonance imaging and US detected a high frequency of thyroid nodules in patients with hyperparathyroidism. This high frequency makes the detection of an intrathyroidal parathyroid adenoma problematic.

Magnetic resonance imaging in acute and subacute mediastinal bleeding.

The appearance of intracranial hematoma on magnetic resonance (MR) images has been described. However, the appearance of hematoma on ECG-gated spin-echo images, which are used for cardiac imaging, has not been described previously. Accordingly a retrospective analysis of nine consecutive patients with acute and subacute mediastinal bleeding imaged with ECG-gated spin-echo MR images was done. The time interval between the incipient event and the date of the MR study was determined, and the signal appearance of the hemorrhage was evaluated relative to striated muscle and fat. MR findings were corroborated by other imaging modalities and surgical findings. Acute hematomas showed medium to high signal intensity, whereas subacute hematomas had areas of high signal intensity on images acquired with ECG gating to every heart beat (repetition time = R-R interval) and a short echo time (30 msec). The characteristic signal intensities of blood on ECG-gated MR images are usually distinct in comparison to other pericardial and mediastinal fluid collections. The ability of MR to specifically identify blood within the first few hours after hemorrhage was not tested in this study.

Cardiac tumors: assessment with Gd-DTPA enhanced MR imaging.

Previous studies have shown the value of MR imaging for the identification of cardiac masses. The distinction of intramural tumors from normal myocardium may be equivocal because of the similarity of signal intensity between tumor and normal myocardium on ECG-gated SE images. The purpose of this study was to assess the role of Gd-DTPA for improving the contrast between cardiac tumors and myocardium. Four patients with established or suspected cardiac tumors were imaged with a 1.5 T imager. The T1-weighted images (TR = RR interval, TE = 20-30 ms) were obtained before and immediately after the intravenous injection of Gd-DTPA, at a dosage of 0.1 mmol/kg. Tumors were identified in three patients. All tumors were isointense to the myocardium in precontrast images but demonstrated differential enhancement relative to myocardium after the administration of Gd-DTPA. Two tumors were hyperintense relative to myocardium, and the third was mostly hypointense, surrounded by a hyperintense rim. In the remaining case, no tumor was found and the myocardium was homogeneously enhanced on postgadolinium images. Gadolinium DTPA can produce differential enhancement of tumor from normal myocardium and therefore demonstrate intramural masses.

Detection of aortic arch thrombus using MR imaging.

Three patients with peripheral embolization and negative echocardiographic examinations were studied with MR imaging. Magnetic resonance imaging detected aortic arch thrombi in the absence of aortic aneurysm, dissection, or ulcerated plaques. By combining spin echo and cine MR sequences, MR enabled us to characterize and contrast intravascular mural thrombi reliably without application of contrast media. Thus we are assisted in the identification of patients at risk for embolization from an often overlooked source: the thoracic aorta.