Protean Manifestations and Diagnostic Challenges Including Discordance Between Electrodiagnostic-Radiologic Studies in Neurolymphomatosis.

INTRODUCTION: Malignant lymphocytic infiltration of the central nervous system (CNS) and peripheral nervous system (PNS) is diagnostically challenging and informs treatment and prognosis. CASE REPORT: We describe the clinical course of a 49-year-old man with CNS and PNS relapse of mantle cell lymphoma and the diagnostic modalities that enabled the diagnosis of neurolymphomatosis. CONCLUSION: This clinical phenotype reinforces previously reported presentations of neurolymphomatosis and the ability of multimodal diagnostics, when combined with clinical suspicion phenotype, to enable diagnosis of malignant lymphocytic infiltration of the CNS and PNS.

Novel Myelin Protein Zero Mutation in 3 Generations of Vermonters With Demyelinating Charcot-Marie-Tooth Disease.

OBJECTIVES: We report the clinical phenotype in 3 consecutive generations with demyelinating Charcot-Marie-Tooth disease that possess a novel sequence variant of myelin protein zero (MPZ). METHODS: Family members from 3 consecutive generations were interviewed, examined, and studied with electrodiagnostic testing. Commercially available next-generation sequencing was performed for the proband. Single-gene analysis was performed for the remaining family members. RESULTS: All patients demonstrated symmetric distal weakness; symmetric distal sensory loss; and diminished deep tendon reflexes. Electrodiagnostic testing was consistent with primary distal demyelination with secondary axon loss. Genetic testing identified a novel base-pair substitution of MPZ (c.314C>T), resulting in a missense variant (p.Pro105Leu). CONCLUSIONS: The novel MPZ base-pair substitution in this family is associated with inherited distal demyelinating neuropathy and should be reclassified as pathogenic for Charcot-Marie-Tooth.

Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium.

SOX transcription factors have the capacity to modulate stem/progenitor cell proliferation and differentiation in a dose-dependent manner. SOX9 is expressed in the small intestine epithelial stem cell zone. Therefore, we hypothesized that differential levels of SOX9 may exist, influencing proliferation and/or differentiation of the small intestine epithelium. Sox9 expression levels in the small intestine were investigated using a Sox9 enhanced green fluorescent protein (Sox9(EGFP)) transgenic mouse. Sox9(EGFP) levels correlate with endogenous SOX9 levels, which are expressed at two steady-state levels, termed Sox9(EGFPLO) and Sox9(EGFPHI). Crypt-based columnar cells are Sox9(EGFPLO) and demonstrate enriched expression of the stem cell marker, Lgr5. Sox9(EGFPHI) cells express chromogranin A and substance P but do not express Ki67 and neurogenin3, indicating that Sox9(EGFPHI) cells are postmitotic enteroendocrine cells. Overexpression of SOX9 in a crypt cell line stopped proliferation and induced morphological changes. These data support a bimodal role for SOX9 in the intestinal epithelium, where low SOX9 expression supports proliferative capacity, and high SOX9 expression suppresses proliferation.