Entity

Time filter

Source Type

Nicosia, Cyprus

Phedonos A.A.P.,The Cyprus Institute of Neurology and Genetics | Shammas C.,The Cyprus Institute of Neurology and Genetics | Skordis N.,The Cyprus Institute of Neurology and Genetics | Skordis N.,Paediatric Endocrine Unit | And 4 more authors.
Clinical Genetics | Year: 2013

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by mutations in the CYP21A2 gene. The carrier frequency of CYP21A2 mutations has been estimated to be 1:25 to 1:10 on the basis of newborn screening. The main objective of this study was to determine the carrier frequency in the Cypriot population of mutations in the CYP21A2 gene. Three hundred unrelated subjects (150 males and 150 females) from the general population of Cyprus were screened for mutations in the CYP21A2 gene and its promoter. The CYP21A2 genotype analysis identified six different mutants and revealed a carrier frequency of 9.83% with the mild p.Val281Leu being the most frequent (4.3%), followed by p.Qln318stop (2.5%), p.Pro453Ser (1.33%), p.Val304Met (0.83%), p.Pro482Ser (0.67%) and p.Met283Val (0.17%). The notable high CYP21A2 carrier frequency of the Cypriot population is one of the highest reported so far by genotype analysis. Knowledge of the mutational spectrum of CYP21A2 will enable to optimize mutation detection strategy for genetic diagnosis of 21-OHD not only in Cyprus, but also the greater Mediterranean region. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source


Skordis N.,Paediatric Endocrine Unit | Skordis N.,The Cyprus Institute of Neurology and Genetics | Shammas C.,The Cyprus Institute of Neurology and Genetics | Efstathiou E.,The Cyprus Institute of Neurology and Genetics | And 3 more authors.
Clinical Biochemistry | Year: 2011

Objectives: The aim of this study was to identify the molecular defect in a group of 37 unrelated Greek Cypriot patients affected by NC-CAH and evaluate the relationship between the genotype, phenotype and adrenal androgen levels. Design and methods: Clinical evaluation, biochemical analysis of 17-OHP, Testosterone, Androstenedione, DHEA-S, direct DNA sequencing and MLPA analyses. Results: Eleven known mutations were identified with the p.V281L being the most predominant and observed in 68.9% of the alleles. There was no difference between the two genotypes (mild/mild and mild/severe) with clinical presentation, whereas a proportional relationship between the type of mutation and adrenal androgen levels was found. Conclusion: The frequency of the underlying genetic defect in our patients with NC-CAH is similar to that observed in most Mediterranean populations. Although the genotype cannot solely explain the clinical expression of NC-CAH, discrimination between mild and severe alleles is crucial in antenatal diagnosis and genetic counselling. © 2011 The Canadian Society of Clinical Chemists. Source


Skordis N.,Paediatric Endocrine Unit
Pediatric endocrinology reviews : PER | Year: 2011

Growth failure in thalassaemia major (TM) has been recognised for many years, and has persisted despite major therapeutic advances. The child with TM has a particular growth pattern, which is relatively normal until age 9-10 years; after this age a slowing down of growth velocity and reduced or absent pubertal growth spurt are observed. The pathogenesis of growth failure is multifactorial. The fundamental problem is the free iron and hemosiderosis-induced damage of the endocrine glands. Additional factors may contribute to the aetiology of growth delay including chronic anaemia and hypoxia, chronic liver disease, zinc and folic acid and nutritional deficiencies, intensive use of chelating agents, emotional factors, endocrinopathies (hypogonadism, delayed puberty, hypothyroidism, disturbed calcium homeostasis and bone disease) and last but not least dysregulation of the GH-IGF-1 axis.Three phases of growth disturbances according to age of presentation are well recognised, and have different aetiologies: in the first phase growth disturbance is mainly due to hypoxia, anaemia, ineffective erythropoiesis and nutritional factors. During late childhood (second phase), growth retardation is mainly due to iron overload affecting GH-IGF-1 axis and other potential endocrine complications. Although appropriate iron chelation therapy can improve growth and development, TM children and adolescents treated intensively with desferrioxamine remain short as well, showing body disproportion between the upper and lower body segment. After the age of 10-11 years (third phase), delayed or arrested puberty is an important contributing factor to growth failure in adolescent thalassaemics, who do not exhibit a normal growth spurt. During the last decades therapeutic progress and bone marrow transplantation resulted in a prolonged life expectancy in TM patients. Growth retardation, however, continues to be a significant challenge in these individuals, often affecting their social adjustment and quality of life. Source


Carre A.,University of Paris Descartes | Rachdi L.,University of Paris Descartes | Tron E.,University of Paris Descartes | Richard B.,University of Paris Descartes | And 6 more authors.
PLoS ONE | Year: 2011

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1-/- mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1-/- mouse embryos showed a significantly smaller total thyroid surface area (-40 to -60%) compared to wild type mice at all study time points (E9.5-E16.5). In both Hes1-/- and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1-/- mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1-/- thyroids revealed a significantly decreased labelling area for T4 (-78%) and calcitonin (-65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (-69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells. © 2011 Carre et al. Source


Habeb A.M.,Paediatric Endocrine Unit | George E.T.,Royal Infirmary | Mathew V.,Royal Infirmary | Hattersley A.L.,Peninsula Medical School
Annals of Saudi Medicine | Year: 2011

The term "maturity onset diabetes of the young" (MODY) describes a heterogeneous group of monogenic diabetes of which hepatic nuclear factor-1 alpha (HNF-1α) MODY is the most common. Patients with HNF-1 mutations typically present after puberty, and oral sulfonylureas (SU) have been shown to be effective in adults with this condition. A 7-year-old boy presented with asymptomatic hyperglycemia ranging between 6.2 and 10.1 mmol/L and glycosuria for nearly a year. The child′s initial HbA1c was 6.9% and the pancreatic Islet cell autoantibodies were negative. His response to the oral glucose tolerance test (OGTT) showed a large increment of glucose from basal level of 7.7 to 21.1 mmol/L in 120 min. The mild presentation, family history, and negative autoantibodies were suggestive of HNF-1α MODY, which was confirmed by mutation analysis. Initial management with diet alone was not sufficient, but he responded well to 20 mg oral gliclazide once a day with an improvement of HbA1C from 7.2% to 6.5% within 3 months of treatment. The case is an illustration of the clinical utility of molecular genetic tests in the management of childhood diabetes. Source

Discover hidden collaborations