Trio-based whole exome sequencing in patients with ectopic posterior pituitary.

Introduction: Ectopic posterior pituitary (EPP) is a rare congenital abnormality, sometimes associated with other midline defects, such as pituitary stalk interruption syndrome (PSIS), in which thin or absent pituitary stalk and anterior pituitary hypoplasia are combined to EPP. Most cases are sporadic, with few reports of familial cases, and many congenital hypopituitarism (CH) cases remain unsolved. Objective: To search for candidate genes associated with this condition, we performed trio-based whole-exome sequencing (WES) on patients with EPP, including two familial cases. Methods: This study included subjects with EPP and PSIS diagnosed by a simple MRI protocol (FAST1.2). We performed two distinct analyses in the trio-based WES. We looked for previously described genes associated with pituitary development. Next, we investigated the whole exome for variants inherited in a pattern consistent with a monogenic etiology. Results: Ten families were evaluated; eight were composed of a child with EPP and healthy parents, one has two affected siblings, and one family has a son and mother with EPP. When analyzing the previously described candidate variants associated with pituitary development, we found variants in GLI2 and FGFR1 in three families. We also found six other variants of interest in three patients: KMT2A, GALR3, RTN4R, SEMA3A, NIPBL, and DSCAML1. Conclusion: The analysis allowed us to find previously reported and not reported GLI2 variants, all inherited from healthy parents, which reinforces the incomplete penetrance pattern of GLI2 variants in the development of EPP and draws attention to possible future functional studies of those variants that have a recurrent expression in CH. We also found novel FGFR1 and SEMA3A variants that suggest an oligogenic mechanism in PSIS and EPP, as seen in patients with hypogonadotropic hypogonadism. We report the first case of a patient with Wiedemann-Steiner syndrome and PSIS, suggesting that the KMT2A gene may be related to pituitary development. Furthermore, the trios' analysis allowed us to find five other variants of interest. Future investigations may clarify the roles of these variants in the etiology of EPP and PSIS.

Influence of Fast Drying on the Morphology of α-Fe2O3 and FeMnO3/α-Fe2O3 Fibers Produced by Solution Blow Spinning.

α-Fe2O3 and FeMnO3/α-Fe2O3 fibers were successfully prepared via Solution Blow Spinning (SBS). The effect of drying during the SBS process on fiber morphology was evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and N2 adsorption-desorption isotherms. A slow drying promoted continuous fibers with rough surfaces and lower average diameters. However, fast drying enabled the production of fibers with low densification and many surface pores with higher BET-specific surface areas. The porous fibers produced have potential applications in energy generation and storage.

High Frequency of Normal Response during GH Stimulation Tests in Patients with Ectopic Posterior Pituitary Gland: A Source of False-Negative Diagnosis of Pituitary Insufficiency.

AIMS: To report false-negative normal growth hormone (GH) peak response in patients with ectopic posterior pituitary gland (EPP) identified with a simplified magnetic resonance imaging (FAST1-MRI). METHODS: We analyzed 75 EPP patients with short stature and reduced growth velocity. Sagittal-T1 imaging (thickness: 2 mm and gap: 0.2 mm) without gadolinium administration was used. A GH peak of ≥5 ng/ml after clonidine or insulin stimulation was considered normal. RESULTS: Normal GH response was observed in 15 of 75 (20%) patients [mean (SDS) peak = 8.2 (4.1) ng/ml]. Age at diagnosis [6.5 (3.0) years vs. 7.8 (4.1) years], gender (10 males/5 females vs. 44 males/16 females), pubertal stage (14 prepubertal/1 pubertal vs. 51 prepubertal/7 pubertal), and target height [-0.4 (0.6) vs. -0.4 (0.9)] were recorded. The perinatal history did not differ between responsive and nonresponsive patients. There was a trend to more frequent multiple hormone deficiency in nonresponsive when compared with responsive patients [3/15 (20%) and 31/60 (51.7%), respectively (p = 0.055)]. Height at diagnosis was lower in nonresponsive patients (p = 0.042). No significant difference in the IGF1 levels (p = 0.598) was observed between the groups. CONCLUSION: Normal GH values after stimulation tests do not exclude EPP-associated GH deficiency. A simplified fast acquisition sagittal-T1 MRI protocol investigation included at the initial diagnostic approach is able to prevent misdiagnosis of GH deficiency in patients with short stature.

Neurocisticercose / Neurocysticercosis

Os autores relatam o caso clínico de um paciente de 24 anos de idade, suinocultor, portador de neurocisticercose. O paciente apresentou um episódio de crise convulsiva e sua tomografia computadorizada de crãnio revelou lesões parenquimatosas sugestivas de neurocisticercose nos quatro estágios da doença (vesicular, vesicular coloidal, granular nodular e nodular calcificado). A neurocisticercose é a doença parasitária mais comum do sistema nervoso, sendo também a causa mais comum de crises epilépticas nos países em desenvolvimento, onde a prevalência das crises é duas vezes maior que nos países desenvolvidos.

It has been reported a clinical case of 24 years-old patient, farmer with neurocysticercosis. The patient presented a epileptic seizure and his computed tomography showed intraparenchymal lesions in the four stages of disease. Neurocysticercosis is the most common parasitic disease of the nervous system in humans and the single most common cause of acquired epileptic seizures in the developing world, where prevalence rates of active epilepsy are twice those in developed countries.