A case series in patients with enteropathy and granulomatous diseases

Background Although sarcoidosis and celiac disease are both chronic immunologic disorders involving multiple organ systems, reports about association of diseases in individual patients are sparse. While sarcoidosis is a chronic granulomatous disease presumably reflecting an exaggerated response to an unknown antigen, celiac disease is a T cell-driven disease triggered by ingestion of gluten, a protein composite found in wheat and related grains. Case presentation We present three cases with a longstanding history of sarcoidosis that have been additionally diagnosed with celiac-like enteropathy. In two cases, celiac disease was established applying celiac- specific serology and duodenal histology, while one case was revealed as an AIE-75-positive autoimmune enteropathy. The HLA-DR3/DQ2 haplotype was confirmed in both celiac patients, hence confirming previous data of linkage disequilibrium as a cause for disease association. Remarkably, one celiac patient presented with granulomatous nodulae in the ileum, thus reflecting an intestinal sarcoid manifestation. In contrast the patient with an autoimmune enteropathy, was HLA-DQ9/DQ6-positive, also arguing against CD. Conclusions Associations of sarcoidosis and celiac disease are rare but do occur. Determining the HLA status in patients with complex autoimmune associations might help classifying involved disease entities

Clinical and Functional Characterization of a Patient Carrying a Compound Heterozygous Pericentrin Mutation and a Heterozygous IGF1 Receptor Mutation

Intrauterine and postnatal longitudinal growth is controlled by a strong genetic component that regulates a complex network of endocrine factors integrating them with cellular proliferation, differentiation and apoptotic processes in target tissues, particularly the growth centers of the long bones. Here we report on a patient born small for gestational age (SGA) with severe, proportionate postnatal growth retardation, discreet signs of skeletal dysplasia, microcephaly and moyamoya disease. Initial genetic evaluation revealed a novel heterozygous IGF1R p.Leu1361Arg mutation affecting a highly conserved residue with the insulin-like growth factor type 1 receptor suggestive for a disturbance within the somatotropic axis. However, because the mutation did not co-segregate with the phenotype and functional characterization did not reveal an obvious impairment of the ligand depending major IGF1R signaling capabilities a second-site mutation was assumed. Mutational screening of components of the somatotropic axis, constituents of the IGF signaling system and factors involved in cellular proliferation, which are described or suggested to provoke syndromic dwarfism phenotypes, was performed. Two compound heterozygous PCNT mutations (p.[Arg585X];[Glu1774X]) were identified leading to the specification of the diagnosis to MOPD II. These investigations underline the need for careful assessment of all available information to derive a firm diagnosis from a sequence aberration

Western Star, 1906-11-21

The Western Star began publication on Newfoundland's west coast on 4 April 1900, appearing weekly with brief semiweekly periods up to 1952, when it became a daily. As of 17 April 2019 it continues as a free weekly community paper

Sequence comparison of the IGF1R carboxyl terminus among different species.

*<p>) amino acid numbering according to human UniProtKB acc. P08069; position of the patient's mutation is marked in bold.</p

IGF1 induced IGF1R phosphorylation and downstream signaling.

<p>A, Wild type and L1361R mutant IGF1R autophosphorylation in transiently transfected R⁻ cells after stimulation with 10 nM IGF1 for 0–30 minutes. Immunoblots were incubated with specific antibodies against phosphorylated IGF1R β-subunit (P-IGF1R), Akt (P-Akt) or Mapk/Erk (P-Mapk/Erk), stripped and subsequently incubated with specific antibodies against the IGF1R α-subunit (IGF1R), Akt (Akt), or Mapk/Erk (Mapk/Erk). IGF1R α-subunit levels were assessed as control of successful transfection. Densitometric units were normalized to total levels of IGF1R α-subunit and the fold increase was calculated (IGF1R-WT at 0 min was set 1). Results are shown as means ± SEM calculated from four independent experiments. B, Yeast two-hybrid analysis of the interaction of the IGF1R derivatives (IGF1R-C-WT, IGF1R-C-L1361R, IGF1R-C-KD) with adapter proteins (IRS1, 14-3-3ß, GIPC, PI3Kp85) by lift-off assay (left panel). Positive interactions led to blue staining (here black) of the colonies. POS, positive control p53 x large T-antigen; NEG, negative control Lamin x large T-antigen. The filter assays shown are representative for more than three independent experiments. Quantification of protein-protein interaction was measured using ONPG-assays and data are shown as mean ± SEM (right panel).</p