EIF2S3 Mutations Associated with Severe X-Linked Intellectual Disability Syndrome MEHMO.

Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c.324T>A; p.Ser108Arg) in another male patient with less severe clinical symptoms. The EIF2S3 gene encodes the γ subunit of eukaryotic translation initiation factor 2 (eIF2), crucial for initiation of protein synthesis and regulation of the ISR. Studies in patient fibroblasts confirm increased ISR activation due to the Ile465Serfs mutation and functional assays in yeast demonstrate that the Ile465Serfs mutation impairs eIF2γ function to a greater extent than tested missense mutations, consistent with the more severe clinical phenotype of the Ile465Serfs male mutation carriers. Thus, we propose that more severe EIF2S3 mutations cause the full MEHMO phenotype, while less deleterious mutations cause a milder form of the syndrome with only a subset of the symptoms.

[Unusual lung finding of massive alveolar filling with foamy macrophages in congenital epidermolysis bullosa after amnion fluid aspiration in 15-day-old newborn without any clinical signs of respiratory impairment]. / Neobvyklý plúcny nález masívneho vyplnenia alveolov penovitými makrofágmi pri kongenitálnej epidermolysis bullosa po aspirácii súcastí plodovej vody u novorodenca prezívajúceho 15 dní bez akýchkolvek príznakov poskodenia dýchacích funkcií.

Epidermolysis bullosa represents a group of mechanobullous diseases which are most commonly genetically determined. We describe the case of a 15-day-old female newborn with congenital epidermolysis bullosa which was inflicted on aproximately 1/3 of her skin surface, who died because of incorrigible sepsis with multiorgan failure. The main topic of our report is a description of an unusual pulmonary finding of massive alveolar filling with foamy macrophages after amnion fluid aspiration, which contained a excessive amount of desquamated epidermal cells. Introduced case shows outstanding discrepancy of negative clinical finding on one side and massive histopathological finding on the other.

[Bart´s syndrome associated with epidermolysis bullosa junctionalis and with pyloric atresia. An autopsy case report]. / Bartov syndróm asociovaný s epidermolysis bullosa junctionalis a s atréziou pyloru. Nekroptická kazuistika.

Barts syndrome, in literature also known under the name CLAS (Congenital Localised Absence of Skin), first described by Bart in 1966 as congenital localized absence of skin, epidermolysis bullosa congenita and nail abnormalities. The authors present a macroscopic and histological findings of a newborn with Barts syndrome, with epidermolysis bullosa junctionalis and atresia pylori, who died 17 days after birth and 13 days after surgery for pyloric stenosis.

Juxtaglomerular cell tumor, causing fetal demise.

AIMS: This case report describes juxtaglomerular cell tumor-a rare renin-producing tumor of the kidney, complicating pregnancy. CLINICAL CASE: A previously healthy 24-year-old primigravid woman developed hypertension in the 20th week of pregnancy, leading to a miscarriage in the 28th week. However, hypertension continued after the miscarriage. A more complete examination revealed a solid tumor in the lower pole of the right kidney. The patient underwent a partial right nephrectomy. A histological examination and electron microscopy confirmed the diagnosis of JGCT. The patient's blood pressure was normalized within 2 weeks. CONCLUSIONS: JGCT can lead to miscarriage if undiscovered during pregnancy. A kidney ultrasound should be performed on pregnant women with newly detected hypertension. No staining in early phase of contrast CT is the feature that differentiates JGCT from renal cell carcinoma. These tumors are benign, with only one reported exception, and nephron-sparing surgery is preferable.