DETECTION OF A RARE MUTATION IN A NOONAN SYNDROME SUSPECTED PATIENT: A CASE REPORT

Noonan syndrome (NS) is a genetic autosomal dominant condition, caused by mutations in PTPN11 and other genes. The aim of this report is to highlight a finding of a rare mutation in the RAF1 gene in a six-year-old child evaluated for Noonan Syndrome. An Ampliseq Research Panel covering A2ML1, BRAF, CBL, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, SOS1 and SPRED1 genes was used on the Ion Torrent platform. Out of 54 variants detected, a single nucleotide missense mutation c.483T>G in the RAF1 gene was classified as likely pathogenic, based on a single previous submission to Clinvar. Further investigations may shed light on the possible role of this variant in the pathogenesis of Noonan Syndrome and other RASopathies

COMPARISON OF ELISA AND CHEMILUMINESCENCE IMMUNOASSAY METHODS FOR QUANTIFICATION OF HUMAN PLACENTAL GROWTH FACTOR IN SERUM

Placental growth factor (PlGF) is crucial during placental development in early pregnancy. Several studies in pregnancies with complications such as preeclampsia or small for gestational age neonates find that PlGF levels are significantly lower in the first trimester, which implies that the concentration of PlGF could be used as an early screening biomarker for these conditions. This study aimed to compare the performance of chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA) for the quantification of human PlGF in serum. This is a comparative study on 88 pregnant women in the first trimester subjected to measurement of PlGF in serum using two commercially available kits: Human PlGF Quantikine HS ELISA (R&D Systems) and PlGF CLIA (Snibe). The overall coefficient of correlation between the tests was 0.93. When the cut-off value of 40 pg/mL was applied, it dropped significantly to 0.50 towards the lower values, while remaining an excellent 0.91 in the group with higher concentrations of PlGF. While R&D Systems’s ELISA seems to have better sensitivity, it is not very convenient to use for a small number of samples. Snibe’s CLIA automated method is user-friendly, fast and powerful. Both tests show excellent performance when indicating risk-free pregnancies

A case of a ten-year old girl with dominantly inherited Familial Mediterranean fever in Republic of Macedonia

The Familial Mediterranean fever (FMF, MIM249100) is an autoimflammatory genetic disease characterized with recurrent painful attacks in the abdomen, chest or joints, usually accompanied with high body temperature. It is classically inherited in an autosomal recessive manner. It is associated with mutations of the MEFV gene, coding for the protein pyrin. More than 140 mutations of the MEFV gene are defined worldwide. Despite the progress in establishing reliable tests practical for routine use, as much as 20% of the patients with FMF remain without a detectable mutation in the MEFV gene. This is the main reason why the diagnosis of FMF remains still a clinical one, according to Tel Hashomer criteria. A 10-year old girl admitted to the Clinic of Pediatrics at the Faculty of Medicine in Skopje for unexplained fever. After numerous laboratory analyses and specialist consultations were done, genetic testing for FMF was requested. The presence of an heterozygous mutation E148Q was confirmed at the Institute for Immunobiology and Human Genetics using a PCR based, reverse hybridization method. Administration of colchicine, the therapy of choice, in a dose of 1.5 mg/day, lead to complete resolution of the symptoms within some days following commencement. Although the disease is classically inherited in a recessive manner, some atypical cases of autosomal dominant inheritance are described. Our patient may be another example supporting the unusual dominant inheritance, since the heterozygous state for the E148Q mutation was the only positive finding in the genotyping of the 12 most frequent MEFV mutations

Immunoglobulin Classes and Subclasses in Macedonian Elderly People Maced

Abstract Aim: The aim of this study was to determine the association of HLA-A, -C and -B genes with ankylosing spondylitis in patients from the Republic of Macedonia. Material and Methods: This study included 307 subjects (250 healthy individuals and 57 patients with ankylosing spondylitis who were diagnosed at the University Clinic of Rheumatology in Skopje). The HLA typing of class 1 (HLA-A, HLA-C and HLA-B) genes was performed using the method of Reverse Line Strip, after isolation of DNK from the blood leucocytes with the standard phenol-chloroforme method. The HLA sub typing of HLA-B*27 was performed with high resolution single-strand polymorphism