Case Report of a Novel NFkB Mutation in a Lymphoproliferative Disorder Patient.

Background: Lymphoproliferative disorders include a heterogeneous list of conditions that commonly involve dysregulation of lymphocyte proliferation resulting in lymphadenopathy and bone marrow infiltration. These disorders have various presentations, most notably autoimmune manifestations, organomegaly, lymphadenopathy, dysgammaglobulinemia, and increased risk of chronic infections.

Case Presentation: A young boy presented with symptoms overlapping different lymphoproliferative disorders, including episodes of chronic respiratory tract infections, dysgammaglobulinemia, lymphadenopathy-associated with splenomegaly as well as skin rashes.

Curation and expansion of Human Phenotype Ontology for defined groups of inborn errors of immunity.

Background: Accurate, detailed, and standardized phenotypic descriptions are essential to support diagnostic interpretation of genetic variants and to discover new diseases. The Human Phenotype Ontology (HPO), extensively used in rare disease research, provides a rich collection of vocabulary with standardized phenotypic descriptions in a hierarchical structure. However, to date, the use of HPO has not yet been widely implemented in the field of inborn errors of immunity (IEIs), mainly due to a lack of comprehensive IEI-related terms.

BCGitis as the primary manifestation of chronic granulomatous disease.

Patients with primary immunodeficiency disease (PID) are not only vulnerable to mycobacterial disease, but are also more likely to develop adverse events following BCG vaccination. These events can range from regional disease (BCGitis) to disseminated disease (BCGosis). Chronic granulomatous disease (CGD), which is characterized by impaired leukocyte phagocytic function, is one of the many inherited PIDs that increase the body's susceptibility to recurrent bacterial and fungal infections.

Novel Frameshift Autosomal Recessive Loss-of-Function Mutation in SMARCD2 Encoding a Chromatin Remodeling Factor Mediates Granulopoiesis.

Purpose: Recently, a new form of congenital neutropenia that is caused by germline biallelic loss-of-function mutations in the SMARCD2 gene was described in four patients. Given the rarity of the condition, the clinical spectrum of the disease has remained elusive. We here report a new patient with a novel frameshift mutation and compare our patient with the previously reported SMARCD2-mutant patients, aiming to provide a more comprehensive understanding of the natural course of the disease.

F-BAR domain only protein 1 (FCHO1) deficiency is a novel cause of combined immune deficiency in human subjects.

FCHO1 deficiency is a novel autosomal recessive combined immune deficiency with impaired clathrin-mediated endocytosis

Author Correction: Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle.

The originally published version of this Article contained an error in Figure 6. In panel b, the top graph (BrdU 21-24d) and the bottom graph (BrdU 28-31d) were inadvertently swapped. This error has now been corrected in both the PDF and HTML versions of the Article.

Author Correction: Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle.

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include support from the CRI Light Microscopy and Image Analysis Core.

Myoblasts and macrophages are required for therapeutic morpholino antisense oligonucleotide delivery to dystrophic muscle.

Exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), employing morpholino antisense oligonucleotides (PMO-AO) to exclude disruptive exons from the mutant DMD transcript and elicit production of truncated dystrophin protein. Clinical trials for PMO show variable and sporadic dystrophin rescue. Here, we show that robust PMO uptake and efficient production of dystrophin following PMO administration coincide with areas of myofiber regeneration and inflammation.

Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA.

Background: Dropped head syndrome is an easily recognizable clinical presentation of Lamin A/C-related congenital muscular dystrophy. Patients usually present in the first year of life with profound neck muscle weakness, dropped head, and elevated serum creatine kinase.

Case Description: Two patients exhibited head drop during infancy although they were able to sit independently.

Homozygous mutation in Atlastin GTPase 1 causes recessive hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is an extremely heterogeneous disease caused by mutations of numerous genes leading to lower limb spasticity (pure forms) that can be accompanied by neurological symptoms (complex forms). Despite recent advances, many causal mutations in patients remain unknown. We identified a consanguineous family with the early-onset HSP.

Males but not females show differences in calbindin immunoreactivity in the dorsal thalamus of the mouse model of fragile X syndrome.

Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of the Fmr1 gene product, fragile X mental retardation protein. Here we analyze the immunohistochemical expression of calcium-binding proteins in the dorsal thalamus of Fmr1 knockout mice of both sexes and compare it with that of wildtype littermates. The spatial distribution pattern of calbindin-immunoreactive cells in the dorsal thalamus was similar in wildtype and knockout mice but there was a notable reduction in calbindin-immunoreactive cells in midline/intralaminar/posterior dorsal thalamic nuclei of male Fmr1 knockout mice.

Ratanhiaphenol III from Ratanhiae radix is a PTP1B inhibitor.

The inhibition of protein tyrosine phosphatase 1B (PTP1B) is considered a valid strategy to combat insulin resistance and type II diabetes. We show here that a dichloromethane extract of Ratanhiae radix ( RR_EX) dose-dependently inhibits human recombinant PTP1B in vitro and enhances insulin-stimulated glucose uptake in murine myocytes. By determination of the PTP1B inhibiting potential of 11 recently isolated lignan derivatives from RR_EX, the observed activity of the extract could be partly assigned to ratanhiaphenol III.

Phenotypic changes in calbindin D28K immunoreactivity in the hippocampus of Fmr1 knockout mice.

Fragile X syndrome (FXS), the most prevalent form of inherited mental retardation, is caused by the lack of FMRP (fragile mental retardation protein) as a result of the transcriptional silencing of the FMR1 gene. Here we analyze the immunohistochemical expression of the calbindin D28K protein in the hippocampus of Fmr1 knockout (KO) mice and compare it with that of their wildtype (WT) littermates. The spatial distribution pattern of calbindin-immunoreactive cells in the hippocampus was similar in WT and KO mice but for each age studied (ranging from 3.

Expression of somatostatin and neuropeptide Y in the embryonic, postnatal, and adult mouse amygdalar complex.

Recent developmental studies indicate that distinct neuronal subpopulations in the amygdala, including somatostatin (SOM)-containing neurons, originate from progenitor domains in the anterior entopeduncular area, thus suggesting a different origin from subpallial territories for amygdalar versus cortical SOM-expressing interneurons, the latter derived from the dorsal part of the medial ganglionic eminence. In this context, we carried out an immunohistochemical study analyzing spatiotemporal expression patterns for SOM- and neuropeptide Y (NPY)-containing neurons in the embryonic, postnatal, and adult mouse amygdala. Our results indicate that SOM- and NPY-immunoreactive cells are present in the amygdalar complex from embryonic day (E)12.

Efferent retinal projections visualized by immunohistochemical detection of the estrogen-related receptor beta in the postnatal and adult mouse brain.

Recently, a new nuclear receptor subfamily has been identified and referred to as estrogen-related receptors. This new group shares sequence similarity, target genes, co-regulatory proteins, and action sites with the estrogen receptors; however, natural estrogens are not estrogen-related receptors ligands. One of the receptors belonging to this group, estrogen-related receptor beta (ERRbeta), is essential for embryo development and is believed to be involved in estrogen-regulated pathways.

Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor.

Pigment epithelium-derived factor (PEDF) is an extracellular multifunctional protein belonging to the serpin superfamily with demonstrable neurotrophic, gliastatic, neuronotrophic, antiangiogenic, and antitumorigenic properties. We have previously provided biochemical evidence for high affinity PEDF-binding sites and proteins in plasma membranes of retina, retinoblastoma, and CNS cells. This study was designed to reveal a receptor involved in the biological activities of PEDF.

Expression patterns of two glutamine synthetase genes in zygotic and somatic pine embryos support specific roles in nitrogen metabolism during embryogenesis.

Here, embryo-specific patterns of glutamine synthetase (GS) genes were studied for the first time using pine somatic and zygotic embryogenesis as model systems. GS1a expression was absent in zygotic embryos whereas it was detected in the cotyledons of somatic embryos at late developmental stages along with transcripts for photosynthesis genes and arginase. These findings suggest that germination was initiated in maturing somatic embryos.