BACKGROUND: Myogenic Arthrogryposis Multiplex Congenita type 3 (AMC-3), is a rare congenital condition characterized by severe hypotonia, club feet, and multiple joint contractures often affecting both arms and legs which start prior to birth.
METHODS: We report a full-term neonate born to first-degree cousins from fourth-generation consanguineous families, who had with antenatal history of reduced fetal movements. At birth, he was noticed to have bilateral club feet, arthrogryposis, severe hypotonia, and absent deep tendon reflexes. The patient developed difficulty in breathing probably attributed to his generalized severe hypotonia, necessitating mechanical ventilation. His creatinine-phospho-kinase, electromyogram, and brain magnetic resonance imaging were normal. Whole-exome sequencing (WES) was requested for the genetic diagnosis of the case. WES identified a novel homozygous variant c.23415-3799C > G p. in the synaptic nuclear envelope protein1 [SYNE1] gene. Seven out of 20 bioinformatic in silico programs predicted a pathogenic effect for this variant. Segregation analysis of the variant in the parents and siblings revealed that both parents and one sibling were heterozygous for the same mutation which proved the variant significance and its autosomal recessive pattern of inheritance.
CONCLUSIONS: AMC3 should be suspected in patients with decreased fetal movements, severe hypotonia, absent deep tendon reflexes, and arthrogryposis. SYNE1 gene mutations can be the underlying genetic defect and molecular genetic testing can prove the diagnosis.

The cell nucleus is becoming increasingly recognized as a mechanosensitive organelle. Most research on nuclear mechanosignaling focuses on the nuclear lamina and coupled actin structures. In this commentary, we discuss the possibility that the nuclear membrane senses and transduces mechanical signals similar to the plasma membrane. We briefly summarize possible (i) pathophysiological sources of nuclear membrane tension, (ii) features that render nuclear membranes particularly suited for mechanotransduction, and (iii) molecular sensing mechanisms.

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of scapulohumeroperoneal muscle weakness, joint contractures, and cardiac defects that include arrhythmias and dilated cardiomyopathy. Although there is a defining group of clinical findings, the proteins responsible and their underlying gene defects leading to EDMD are varied. A common aspect of the gene defects is their involvement in, or with, the nuclear envelope. Treatment approaches are largely based on clinical symptoms. The genetic diversity of EDMD predicts that a cure will ultimately depend upon the individual\'s defect at the gene level, making this an ideal candidate for a precision medicine approach.

A pregnancy with conjoined twins was observed after transfer of a multinuclear embryo. As nuclear mechanisms have a role in cellular differentiation, association between multinucleation and fetal malformations is possible. Follow-up studies on children born after transfer of embryos with bi/multinuclear blastomeres are needed.

In this study, we focus our interest on some peculiar infrastructural abnormalities detected in an insulinoma case. Tumor pancreatic endocrine cells proliferated detrimental to exocrine counterpart, so that extensive areas of prevalent β-tumor cells can be seen. Two phenotypes of β-tumor cells can be identified: (1) β-tumor cells with full euchromatic and nucleolated nuclei and (2) β-tumor cells with heterochromatic and shrink nuclei. Because of stroma alteration, including basement membrane, cell-extracellular matrix junctions are also compromised. The mostly striking and important finding in this report for a case of insulinoma is the high fragility of plasma membrane of both two phenotypes of β-tumor cells. Cell-cell junctions, especially desmosomal junctions are severely altered, almost missing, plasma membranes showed shedding membrane vesicles and extensive dissolutions leading to pseudo-syncytia formation. Extravasated blood cells, including inflammatory cells contribute to the dramatic and extensive destructive areas of epithelial cells as well as stroma counterpart. Moreover, also the inner cell cytomembranes exhibit abnormalities: many β-tumor cells have excessive dilatations of nuclear envelope and endoplasmic reticulum. All above severe infrastructural abnormalities, especially down regulation of cell-cell and cell-extracellular matrix adhesions and plasma membranes fragility might result in aberrant cell behavior and, consequently, much care should be taken for the postoperatory patient evolution.

Mutations in the LMNA gene are associated with a spectrum of human dystrophic diseases termed the \"nuclear laminopathies.\" We recently found that the accumulation of the inner nuclear envelope proteins SUN1 is pathogenic in progeric and dystrophic laminopathies. This conclusion arose from the unexpected observation that the deletion of Sun1, instead of accelerating aging, actually ameliorated the progeric and dystrophic phenotypes in Lmna-deficient mice. In human cells, knocking down SUN1 corrected the nuclear aberrancies and the senescent tendencies of HGPS (Hutchinson-Gilford progeria syndrome) skin fibroblasts. Here we offer additional comments on the contributions of SUN1 and the process of normal protein turnover to cellular aging.

Planctomycetes, Verrucomicrobia and Chlamydia are prokaryotic phyla, sometimes grouped together as the PVC superphylum of eubacteria. Some PVC species possess interesting attributes, in particular, internal membranes that superficially resemble eukaryotic endomembranes. Some biologists now claim that PVC bacteria are nucleus-bearing prokaryotes and are considered evolutionary intermediates in the transition from prokaryote to eukaryote. PVC prokaryotes do not possess a nucleus and are not intermediates in the prokaryote-to-eukaryote transition. Here we summarise the evidence that shows why all of the PVC traits that are currently cited as evidence for aspiring eukaryoticity are either analogous (the result of convergent evolution), not homologous, to eukaryotic traits; or else they are the result of horizontal gene transfers.

BACKGROUND: Adamantinoma is a rare primary bone neoplasm of low malignant potential that may recur or metastasize in a mall percentage of patients. The myriad histologic patterns may cause difficulty in distinguishing this tumor from other primary or metastatic neoplasms. The cytomorphologic findings of fine needle aspiration biopsy were reported previously in only a small number of cases.
METHODS: A 32-year-old man presented with a mass in the distal side of the left leg that was diagnosed as classic adamantinoma by open biopsy. Local recurrence and pulmonary metastases were confirmed by fine needle aspiration biopsy, which showed low grade, uniform cells with nuclear membrane grooves. The patient underwent a below-the-knee amputation and is receiving palliative treatment for progressive pulmonary spread.
CONCLUSIONS: The diagnosis of adamantinoma requires knowledge of compatible clinical and radiologic studies as well as understanding of the variable histologic patterns that one may encounter. Fine needle aspiration biopsy is particularly useful in the diagnosis of recurrent and metastatic adamantinoma. This case report describes a distinctive cytomorphologic feature of nuclear grooves that may be a useful aid in distinguishing the tumor cells of adamantinoma from other cell types.

The cytologic appearance of endosalpingiosis in peritoneal fluid cytology smears has not been extensively described. We report a case of endosalpingiosis in a 29-year-old pregnant female who presented with peritoneal fluid. Dense papillary epithelial clusters with indistinct ciliated cells were found in the Papanicolaou-stained smears. However, long and delicate cilia were obvious in papillary cluster with scanning electron microscopy. Cell nuclei were oval, with finely dispersed chromatin and uniform nuclear membrane. Peritoneal fluid cytology with these findings may be helpful to suggest the probable preoperative diagnosis of endosalpingiosis or benign glandular inclusions involving the pelvic peritoneum.

A case of autosomal dominant limb-girdle muscular dystrophy with atrioventricular conduction block (LGMD1B) has been documented. In this family, 13 members, nine males and four females, had cardiac arrhythmia requiring pacemakers. The proband, a 67-year-old male, had longstanding proximal muscle weakness later associated with cardiac arrhythmia but showed neither rigid spine nor joint contracture. His muscle enzymes were within normal range and muscle biopsy showed myopathic changes. Gene analysis of the proband revealed Tyr481His mutation in the exon 8 of lamin A/C (LMNA) gene which is adjacent to the codon mutated in reported cases of familial partial lipodystrophy. This is the first report of muscular dystrophy shown to have a mutation of LMNA in a Japanese family as well as the first case of missense mutation in the exon 8 with LGMD1B phenotype.