Insulinoma presenting as hypoglycemia during lactose tolerance testing: a case report.

Background: Insulinoma is a rare functioning pancreatic endocrine tumor, typically presenting as a sporadic solitary lesion causing hypoglycemia. While these tumors can lead to marked autonomic and neuroglycopenic symptoms, the diagnosis is often delayed.

Case Presentation: We present a case of a 60-year-old Caucasian man presenting with a 1-year history of progressive episodic confusion and an unexpected finding of symptomatic hypoglycemia during a lactose tolerance test.

Comparing Pathology Report Quality Indicators in 2 Distinct Whipple Resection Specimen Protocols.

Objectives: Pancreaticoduodenectomy specimens are complex, with varying gross examination techniques. In 2012, our institution began using axial sectioning. We sought to determine if this resulted in more complete pathology reporting.

Atypical Hepatic Mesenchymal Hamartoma: Histologic Appearance, Immunophenotype, and Molecular Findings.

Hepatic mesenchymal hamartoma is a rare benign neoplasm principally encountered in young children. Its origin is unknown. We report an unusual hepatic mesenchymal hamartoma in a 7-month-old girl, including histopathologic findings, immunophenotype, and karyotype.

A Mild PUM1 Mutation Is Associated with Adult-Onset Ataxia, whereas Haploinsufficiency Causes Developmental Delay and Seizures.

Certain mutations can cause proteins to accumulate in neurons, leading to neurodegeneration. We recently showed, however, that upregulation of a wild-type protein, Ataxin1, caused by haploinsufficiency of its repressor, the RNA-binding protein Pumilio1 (PUM1), also causes neurodegeneration in mice. We therefore searched for human patients with PUM1 mutations.

Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis.

Encephalocraniocutaneous lipomatosis (ECCL) is a sporadic condition characterized by ocular, cutaneous, and central nervous system anomalies. Key clinical features include a well-demarcated hairless fatty nevus on the scalp, benign ocular tumors, and central nervous system lipomas. Seizures, spasticity, and intellectual disability can be present, although affected individuals without seizures and with normal intellect have also been reported.

Receptor tyrosine kinase mutations in developmental syndromes and cancer: two sides of the same coin.

Receptor tyrosine kinases (RTKs) are a family of ligand-binding cell surface receptors that regulate a wide range of essential cellular activities, including proliferation, differentiation, cell-cycle progression, survival and apoptosis. As such, these proteins play an important role during development and throughout life; germline mutations in genes encoding RTKs cause several developmental syndromes, while somatic alterations contribute to the pathogenesis of many aggressive cancers. This creates an interesting paradigm in which mutation timing, type and location in a gene leads to different cell signaling and biological responses, and ultimately phenotypic outcomes.

The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome.

Background: Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive.

Mutations in STAMBP, encoding a deubiquitinating enzyme, cause microcephaly-capillary malformation syndrome.

Microcephaly-capillary malformation (MIC-CAP) syndrome is characterized by severe microcephaly with progressive cortical atrophy, intractable epilepsy, profound developmental delay and multiple small capillary malformations on the skin. We used whole-exome sequencing of five patients with MIC-CAP syndrome and identified recessive mutations in STAMBP, a gene encoding the deubiquitinating (DUB) isopeptidase STAMBP (STAM-binding protein, also known as AMSH, associated molecule with the SH3 domain of STAM) that has a key role in cell surface receptor-mediated endocytosis and sorting. Patient cell lines showed reduced STAMBP expression associated with accumulation of ubiquitin-conjugated protein aggregates, elevated apoptosis and insensitive activation of the RAS-MAPK and PI3K-AKT-mTOR pathways.

The abundance of processed pseudogenes derived from glycolytic genes is correlated with their expression level.

The abundance of processed pseudogenes in different vertebrate species is known to be proportional to the length of their oogenesis. However, this hypothesis cannot explain why, in a given species, certain genes produce more processed pseudogenes than others. In particular, one would expect that all genes of the glycolytic pathway would generate roughly the same number of processed pseudogenes.

17p13.3 microduplications are associated with split-hand/foot malformation and long-bone deficiency (SHFLD).

Split-hand/foot malformation with long-bone deficiency (SHFLD) is a relatively rare autosomal-dominant skeletal disorder, characterized by variable expressivity and incomplete penetrance. Although several chromosomal loci for SHFLD have been identified, the molecular basis and pathogenesis of most SHFLD cases are unknown. In this study we describe three unrelated kindreds, in which SHFLD segregated with distinct but overlapping duplications in 17p13.