Przeprowadzona z wykorzystaniem zależnej od ligacji multipleksowej amplifikacji sond analiza genów KAL1, GNRH1, GNRHR, PROK2 i PROKR2 u pacjentów płci męskiej z idiopatycznym hipogonadyzmem hipogonadotropowym

Introduction: The purpose of this study was to determine the prevalence of KAL1, GNRH1, GNRHR, PROK2, and PROKR2 copy numbervariations in patients with idiopathic hypogonadotropic hypogonadism (IHH).Material and methods: 86 hypogonadal males (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism [nIHH] andten with Kallmann syndrome [KS]) and 95 healthy control individuals were studied for the presence of aforementioned genomic rearrangements,using multiplex ligation dependent probe amplification (MLPA).Results: We detected that of the 86 patients, three with KS had a deletion of the KAL1 gene in exon 9, one of whom also carried a duplicationin exon 11; and three with nIHH had a duplication of the PROK2 gene in exon 3; a deletion of the GNRHR gene in exon 1; anda duplication of the same gene in exon 2, respectively. No abnormalities were found in the patient group for the PROKR2 and GNRH1genes. In addition, no genomic rearrangements were identified in the healthy control individuals for the described genes.Conclusions: Defining the genetic basis of disease is essential to improve our understanding of this complex disorder, and could be usefulfor genetic counselling and for directing therapy. In addition, discovering the association between genetic mutations and disease isimportant for our better understanding of normal reproductive functions.Wstęp: Celem badania było ustalenie rozpowszechnienia zmienności liczby kopii genów KAL1, GNRH1, GNRHR, PROK2 i PROKR2u pacjentów z idiopatycznym hipogonadyzmem hipogonadotropowym (IHH, idiopathic hypogonadotropic hypogonadism).Materiał i metody: Obecność wymienionych wyżej rearanżacji genomowych zbadano metodą zależnej od ligacji multipleksowej amplifikacjisond (MLPA, multiplex ligation dependent probe amplification) u 86 mężczyzn z hipogonadyzmem — w tym u 76 z rozpoznaniemIHH przebiegającego bez zaburzeń węchu (nIHH, normosmic idiopathic hypogonadotropic hypogonadism) i u 10 z rozpoznaniem zespołuKallmanna (KS, Kallmann syndrome) — oraz u 95 zdrowych osobników kontrolnych.Wyniki: U 3 pacjentów z KS stwierdzono delecję w obrębie genu KAL1 w egzonie 9, przy czym u jednego z nich występowała też duplikacjaw egzonie 11. Z kolei łącznie u 3 pacjentów z nIHH stwierdzono: duplikację w obrębie genu PROK2 w egzonie 3 u jednego pacjenta,delecję w obrębie genu GNRHR w egzonie 1 u drugiego pacjenta oraz duplikację obrębie tego samego genu w egzonie 2. Jeśli zaś chodzi ogeny PROKR2 i GNRH1, to w grupie pacjentów nie stwierdzono żadnych nieprawidłowości w tym zakresie. Nie stwierdzono też żadnychrearanżacji genomowych w zakresie wymienionych genów u zdrowych osobników kontrolnych.Wnioski: Określanie podłoża genetycznego ma ogromne znaczenie dla pogłębiania wiedzy na temat tej złożonej choroby i możebyć przydatne w poradnictwie genetycznym i ustalaniu leczenia. Ponadto odkrywanie powiązań pomiędzy mutacjami genetycznymia omawianą chorobą ma duże znaczenie dla pogłębiania wiedzy na temat prawidłowego funkcjonowania układu rozrodczego

Do the Changes in the Serum Levels of IL-2, IL-4, TNFα, and IL-6 Reflect the Inflammatory Activity in the Patients with Post-ERCP Pancreatitis?

Background. Acute pancreatitis is the major complication of endoscopic retrograde cholangiopancreatography (ERCP) procedure and there are some reports showing cytokine changes in ERCP-induced pancreatits. Goals. To investigate the association between early changes (within 24 hours) in the serum interleukin (IL)-2, IL-4, tumor necrosis factor (TNF)α, and IL-6 levels and the development of post-ERCP pancreatitis. Study. Forty five consecutive patients who underwent therapeutic ERCP and 10 patients with acute pancreatitis without ERCP were enrolled to the study. Serum concentrations of IL-2, IL-4, TNFα, and IL-6 were determined immediately before, 12 hours and 24 hours after ERCP. Results. Seven of the 45 patients (15.5%) developed post-ERCP pancreatitis. The levels of IL-4 at 24 hours after ERCP were significantly lower in the patients with post-ERCP pancreatitis than in those without pancreatitis, while TNFα levels at 12 hours after ERCP were higher in the complicated group than those of the uncomplicated group. The ratios of TNFα/IL-4 at 12 and 24 hours after ERCP were found significantly higher in the patients with post-ERCP pancreatitis than in those without pancreatitis. IL-6 in the complicated patients was found significantly increased at 24 hours after ERCP. Conclusions. The enhancement of serum TNFα and IL-6 levels in the patients with ERCP-induced pancreatitis reflects the inflammatory activity. Additionally, these cytokines together with IL-4 can be used in clinical laboratory monitoring of ERCP

Pro- and Anti-Inflammatory Cytokine Balance in Major Depression: Effect of Sertraline Therapy

The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-α, TGF-β1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-α) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-β1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-β1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment

A Case of Common Variable Immunodeficiency with CREBP Gene Mutation without Rubinstein Taybi Syndrome Features

Hypogammaglobulinemias, based on inborn errors of immunity, are primary immunodeficiencies (PIDs) that can also be diagnosed for the first time in adulthood. Common variable immunodeficiency (CVID) is a multifactorial disease often symptomatic due to antibody deficiency. In addition, some PIDs are classified into the category of immunodeficiencies with syndromic features due to their accompanying clinical findings unrelated to immunity. In this article, a patient with CVID who was diagnosed in adulthood and who was revealed to have a mutation specific to Rubinstein–Taybi syndrome and clinical features reminiscent of this syndrome only after molecular tests was presented

Coexistence of a Leaky SCID Phenotype With Hyperphenylalaninemia in an Adult Case

In recent years, due to the widespread use of advanced molecular diagnostic methods, it has become clear that individuals in particular born from consanguineous marriages may be carriers of different genetic diseases. For this reason, cases where diseases related to inborn errors of immunity (IEI) and metabolism errors are detected in the same patient are encountered more frequently. In patients affected by different genetic defects, the pathophysiology is more complex, and disease management is more difficult. In this article, we aimed to draw attention to this complex genetic carrier state in a male with primary immunodeficiency (PID). In the patient who presented with recurrent lower respiratory tract infections, bronchiectasis, asthma and nasal polyps, and antibody deficiencies as well as cellular immunodeficiency findings were detected in the immunological analyses. In the whole exome sequencing (WES) study, three different variants were detected, two in genes related to PIDs (DCLRE1C and TNFRSF13B) and one in the gene related to phenylalanine metabolism (phenylalanine hydroxylase (PAH)). In the light of the current findings, the patient was evaluated as having leaky severe combined immunodeficiency (SCID) with immune phenotype T−B−natural killer (NK)+ and hyperphenylalaninemia (HPA). This case showed us that metabolic diseases may accompany a delay in the diagnosis of SCID and patients should be evaluated with a multidisciplinary approach

A Case of Common Variable Immunodeficiency with CREBP Gene Mutation without Rubinstein Taybi Syndrome Features

Hypogammaglobulinemias, based on inborn errors of immunity, are primary immunodeficiencies (PIDs) that can also be diagnosed for the first time in adulthood. Common variable immunodeficiency (CVID) is a multifactorial disease often symptomatic due to antibody deficiency. In addition, some PIDs are classified into the category of immunodeficiencies with syndromic features due to their accompanying clinical findings unrelated to immunity. In this article, a patient with CVID who was diagnosed in adulthood and who was revealed to have a mutation specific to Rubinstein–Taybi syndrome and clinical features reminiscent of this syndrome only after molecular tests was presented.</jats:p