Emine Yaykasli

Whole-Exome Sequencing Identifies Homozygous GPR161 Mutation in a Family with Pituitary Stalk Interruption Syndrome

CONTEXT Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. OBJECTIVE We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk-characteristic clinical diagnostic findings of PSIS. DESIGN AND PARTICIPANTS WES was applied to two affected and one unaffected siblings. RESULTS WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. CONCLUSION Mutations of GPR161 may be implicated as a potential novel cause of PSIS.

Leptin induces ADAMTS-4, ADAMTS-5, and ADAMTS-9 genes expression by mitogen-activated protein kinases and NF-ĸB signaling pathways in human chondrocytes.

Elucidation of the causes of inflammation has vital importance in the development of new approaches for the treatment of arthritic diseases. The degradation of aggrecan by upregulated disintegrin and metalloproteinase with trombospondin motifs (ADAMTSs) is the key event in the development of both rheumatoid arthritis (RA) and osteoarthritis (OA). Increased levels of leptin in both RA and OA have been demonstrated, thus linking leptin to arthritic diseases, but the mechanism has not been clarified. This study investigated the putative role of signaling pathways (p38, JNK, MEK1, NF‐ĸB, and PI3) involved in leptin‐induced cartilage destruction. Normal human articular chondrocytes were cultured with recombinant human leptin at 100, 250, 500, and 1000 ng/mL doses for 6, 12, 24, and 48 h, after which ADAMTS‐4, ‐5, and ‐9 genes expression were determined by real time‐polymerase chain reaction (RT‐PCR) and Western Blot methods. The signaling pathways involved in leptin‐induced ADAMTSs upregulation were also investigated by using inhibitors of signaling pathways. It was demonstrated that ADAMTSs expression level was peaked at 1000 ng/mL doses for 48 hours, and MAPKs (p38, JNK, and MEK) and NF‐ĸB signaling pathways involving in leptin triggered ADAMTSs upregulation. Obesity as a risk for RA and OA may contribute to the inflammation of both RA and OA diseases by secreting adipokines like leptin. We hypothesize that leptin is involved in the development of RA and OA accompanied with obesity by increasing ADAMTS‐4, ‐5, and ‐9 genes expression via MAPKs and NF‐ĸB signaling pathways.

Omentin serum levels and omentin gene Val109Asp polymorphism in patients with psoriasis

Psoriasis is a chronic inflammatory disease of uncertain pathogenesis. Omentin is a new adipokine with anti‐inflammatory properties; however, the relationship between psoriasis and omentin has not been fully established yet.

Effect of adiponectin on a disintegrin and metalloproteinase with thrombospondin motifs-9 gene expression in human chondrocytes (CCR5P.257)

A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a family of peptidases. They comprise 19 members, and have several vital functions in organism. ADAMTS-9 with aggrecanolytic activity is responsible for the degradation of the articular cartilage components like aggrecan. Adiponectin is the most abundantly secreted adipokines (adipocytokines), and the characteristic of adiponectin is controversial. It was assumed that adiponectin has anti-inflammatory effect. However, recent studies showed the inflammatory features of adiponectin. It was aimed to evaluate the effect of adiponectin on ADAMTS-9 gene expression in human chondrocytes. Human articular chondrocytes were cultured and exposed by adiponectin at 1, 4, 8 and 12 µg/ml doses. At the end of the incubation, total RNA was reverse-transcribed by random primer. The expression levels of the ADAMTS-9 and β-actin genes were determined using real-time polymerase chain reaction. The ADAMTS-9 gene expression was found to increase after adiponectin incubation at 12 µg/ml dose. The interleukin-1β induced ADAMTS-9 gene up-regulation and the increased serum level of ADAMTS-9 in patients with osteoarthritis (OA) were reported before. Similarly, the putative involvement of adiponectin in OA and rheumatoid arthritis (RA) was demonstrated. Together with these findings, our results suggesting that adiponectin may involve in the degradation of aggrecan by increasing ADAMTS-9 gene expression.