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Paphos, Cyprus

Neocleous V.,The Cyprus Institute of Neurology and Genetics | Costi C.,The Cyprus Institute of Neurology and Genetics | Kyriakou C.,The Cyprus Institute of Neurology and Genetics | Kyriakides T.C.,Yale University | And 17 more authors.
Annals of Human Genetics | Year: 2015

Familial Mediterranean fever (FMF) is caused by mutations in the MEFV gene and the spectrum of mutations among Greek-Cypriots with FMF-related symptoms was examined. Sequence analysis for exons 2, 3, 5, and 10 of the MEFV gene was performed in a cohort of 593 patients. A total of 70 patients carried mutations in the homozygote or compound heterozygote state, 128 were identified with one MEFV mutation and 395 had no mutations. Of the 268 identified alleles, p.Val726Ala (27.61%) was the most frequent followed by p.Met694Val (19.40%). The missense mutations p.Arg761His (3.73%) and p.Ala744Ser (2.24%) were identified as the rarest. An interesting finding is the high frequency (18.28%) of the complex p.Phe479Leu-p.Glu167Asp that was identified in 49 of the mutated alleles. The MEFV genotypes did not follow a binomial distribution and proved not to satisfy the HWE (P < 0.001). The high percentage (66.61%) of patients with unidentified mutations could be due to mutations in the rest of the coding or noncoding MEFV gene or due to mutations in other genes that are also causing Hereditary Recurrent Fevers. Results from this work indicate the high incidence of FMF in Cyprus and describe the spectrum of the mutations which occur in the country. © 2014 John Wiley & Sons Ltd/University College London. Source

Toumba M.,Iasis Hospital | Toumba M.,Paediatric Endocrine Unit | Kokotsis V.,Paediatric Endocrine Unit | Savva S.C.,Research and Education Institute of Child Health | And 3 more authors.
Journal of Pediatric Endocrinology and Metabolism | Year: 2014

Objective: The combination therapy of gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) has been used to increase growth in children with premature sexual maturation and attenuated growth. The aim of this report was to study the benefit over cost of combined treatment in girls with central precocious puberty (CPP) and poor height prognosis and in girls with idiopathic short stature (ISS) and early puberty. Should this expensive treatment be given to such patients? Subjects and methods: Two patient groups were included: five girls with central precocious puberty (CPP) who reached final height (FH) at 16.3±1.2 years and eight girls with ISS who reached FH at 14.7±0.8 years. Patients were treated for 3.5±0.6 years. Results: In both groups, FH improved significantly; in CPP from -1.3 to -0.5 standard deviation score (SDS) (p=0.030) and in ISS from -2.6 to -1.7 SDS (p=0.012). Only girls with CPP reached their target height (-0.5 vs. -0.6 SDS) (p=0.500). Conclusions: Both groups had a total height gain of 5 cm. Each centimetre cost about €2700 per patient. This treatment should be considered only in patients with extremely low height prediction and very early pubertal onset. © 2014 by Walter de Gruyter Berlin Boston 2014. Source

Toumba M.,Iasis Hospital
Georgian medical news | Year: 2012

Until recently, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) were considered to control only linear growth. Apart from growth effect, GH has additional important physiological functions in the human body influencing several metabolic processes, body composition, muscle strength, and bone mineral density. In adolescence, where the majority of these physiological functions reach a zenith, GH plays a crucial role. The ability of GH to trigger cardiac muscle growth by direct and indirect effects plays a pivotal role in the physiology of the heart. Patients with childhood or adulthood onset of GH deficiency are exposed to increased risk for cardiovascular morbidity. GH treatment may have beneficial effect on the cardiovascular system in GH deficient adolescents. On the other hand discontinuation of GH treatment in these patients may result in the accumulation of relevant cardiovascular risk factors such as increase in body and abdominal fat and LDL and total cholesterol concentrations. No potential adverse cardiac effects of GH therapy have been so far demonstrated in short stature patients with normal GH secretion. Nevertheless, no evidence of heart hypertrophy or cardiomypathy has been documented in adolescents with GH excess has been reported in adults. Nonetheless, normalization of GH and IGF-1 levels in such patients is essential in order to arrest cardiovascular disease later in life. Source

Skordis N.,Cyprus Institute of Neurology and Genetics | Skordis N.,Paedi Center for Specialized Pediatrics | Skordis N.,University of Nicosia | Shammas C.,Cyprus Institute of Neurology and Genetics | And 6 more authors.
Journal of Endocrinological Investigation | Year: 2015

Objectives: To seek evidence on the prevalence of CYP21A2 genetic defects and consequences in girls with premature adrenarche (PA). Methods: The study included 59 girls diagnosed with PA. Direct DNA sequencing and MLPA analysis were performed to identify mutations in CYP21A2 gene. Results: Twelve girls were diagnosed with non-classic congenital adrenal hyperplasia (NC-CAH) based on stimulated 17-hydroxyprogesterone (17-OHP) levels and the presence of two mutations in CYP21A2, 19 were heterozygotes. The most frequent mutations detected were the mild p.Val281Leu and p.Pro453Ser. Higher levels of mean stimulated 17-OHP were found in the carriers of the p.Val281Leu mutation. The detection rate for two CYP21A2 mutations was higher in girls with PA than in adult females with hyperandrogenemia in our studied population. A notable increased allelic frequency for the known p.Asn493Ser polymorphism was observed in the pool of the 28 girls with PA in whom no mutation was identified. Conclusions: In girls with PA, the frequency of the underlying CYP21A2 genetic defects is similar to that observed in other populations. The carrier status is likely a contributing factor in the genotype-phenotype correlation in NC-CAH. However, polymorphisms and other genes may be implicated in the clinical manifestation of the disease. © 2014 Italian Society of Endocrinology (SIE). Source

Toumba M.,Iasis Hospital | Neocleous V.,Cyprus Institute of Neurology and Genetics | Shammas C.,Cyprus Institute of Neurology and Genetics | Anastasiadou V.,Cyprus Institute of Neurology and Genetics | And 6 more authors.
Journal of Pediatric Endocrinology and Metabolism | Year: 2013

Objectives: Camurati-Engelmann disease (CED) is a rare form of progressive diaphyseal dysplasia as a result of mutations in the transforming growth factor gene TGFbeta1 on chromosome 19q13.1-q13.3. Endocrine complications such as osteoporosis, vitamin D deficiency, delayed puberty, and hypogonadotrophic hypogonadism may be present. Methods: Genetic analysis of the TGFbeta1 gene revealed a heterozygous missense mutation p.R218C in exon 4 of chromosome 19q13.1-q13.3 in a 14-year-old girl who presented with typical symptoms of CED, hyperprolactinaemia, and menstrual irregularity. Results: The patient responded well to prednisone 5 mg/kg/day, as well as calcium and vitamin D supplements. Conclusions: The role of p.R218C in TGFbeta1 on the mechanism of the disease, and the complications of it in bones and endocrine glands, remains unclear. Early recognition as well as a detailed understanding of the pathogenesis of the disease are important for future treatment options and a better quality of life of such patients. Source

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