Cyprus Paediatric Neurology Institute

Nicosia, Cyprus

Cyprus Paediatric Neurology Institute

Nicosia, Cyprus
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Georgiou T.,The Cyprus Institute of Neurology and Genetics | Ho G.,University of Sydney | Vogazianos M.,The Center for Preventive Paediatrics | Dionysiou M.,The Cyprus Institute of Neurology and Genetics | And 6 more authors.
Clinical Biochemistry | Year: 2012

Objectives: The purpose of this study was to identify the mutations responsible for phenylalanine hydroxylase deficiency in Cypriot patients detected through neonatal screening. Design and Methods: Analysis of the PAH gene was performed by direct sequencing of the patients' genomic DNA, MLPA analysis and real-time PCR. Results: Among 22 independent alleles thirteen previously described mutations were detected (detection rate 100%), all in compound heterozygosity: p.Arg395Gly (18.2%), c.168+5G>C (13.6%), p.EX3del (9%), c.1066-11G>A (9%), p.Ala403Val (9%), p.Glu178Gly (9%), p.Ser70Pro (4.5%), p.Arg241His (4.5%), p.Phe55fs (4.5%), p.Arg158Gln (4.5%), p.Asp222Gly (4.5%), p.Ala300Ser (4.5%), p.Pro225Thr (4.5%). Of the ten different genotypes, three have been previously reported to be associated with a mild clinical phenotype and to respond to tetrahydrobiopterin (BH 4) administration. Conclusions: Marked genetic heterogeneity was found in Cypriot patients with hyperphenylalaninemia with two mutations accounting for 32% of the alleles. Most of the mutations detected have been found in other European and Mediterranean populations. © 2012 The Canadian Society of Clinical Chemists.


Georgiou T.,The Cyprus Institute of Neurology and Genetics | Christopoulos G.,The Cyprus Institute of Neurology and Genetics | Anastasiadou V.,Archbishop Makarios III Hospital | Hadjiloizou S.,Cyprus Paediatric Neurology Institute | And 5 more authors.
Meta Gene | Year: 2014

Tay-Sachs disease (TSD) is a recessively inherited neurodegenerative disorder caused by mutations in the HEXA gene resulting in β- hexosaminidase A (HEX A) deficiency and neuronal accumulation of GM2 ganglioside. We describe the first patient with Tay-Sachs disease in the Cypriot population, a juvenile case which presented with developmental regression at the age of five. The diagnosis was confirmed by measurement of HEXA activity in plasma, peripheral leucocytes and fibroblasts. Sequencing the HEXA gene resulted in the identification of two previously described mutations: the nonsense mutation c.78G>A (p.Trp26X) and the silent mutation c.1305C>T (p.=). The silentmutation was reported once before in a juvenile TSD patient of West Indian origin with an unusually mild phenotype. The presence of this mutation in another juvenile TSD patient provides further evidence that it is a disease-causing mutation. Successful preimplantation genetic diagnosis (PGD) and prenatal follow-up were provided to the couple. © 2014 The Authors.


Georgiou T.,The Cyprus Institute of Neurology and Genetics | Nicolaidou P.,Cyprus Paediatric Neurology Institute | Hadjichristou A.,Archbishop Makarios III Hospital | Ioannou R.,The Cyprus Institute of Neurology and Genetics | And 5 more authors.
Clinical Biochemistry | Year: 2014

Objectives: The purpose of this study was to identify the mutations in the glutaryl-CoA dehydrogenase gene (. GCDH) in ten Cypriot patients with Glutaric aciduria type I (GAI). Design and methods: Molecular analysis of the GCDH gene was performed by direct sequencing of the patients' genomic DNA. In silico tools were applied to predict the effect of the novel variants on the structure and function of the protein. Results: All disease alleles were characterized (mutation detection rate 100%). Five missense mutations were identified: c.192G. >. T (p.Glu64Asp) and c.803G. >. T (p.Gly268Val), which are novel, and three previously described mutations, c.1123T. >. C (p.Cys375Arg), c.1204C. >. T (p.Arg402Trp) and c.1286C. >. T (p.Thr429Met). Conclusions: Two novel mutations, p.Glu64Asp and p.Gly268Val, account for the majority of disease alleles (76.5%) in Cypriot patients with Glutaric aciduria type I. A founder effect for the p.Glu64Asp and the p.Gly268Val can be suggested based on the place of origin of the carriers of these mutations. Identification of the causative mutations of GAI in Cypriot patients will facilitate carrier detection as well as post- and pre-natal diagnosis. © 2014 The Canadian Society of Clinical Chemists.


PubMed | The Cyprus Institute of Neurology and Genetics, Archbishop Makarios III Hospital and Cyprus Paediatric Neurology Institute
Type: Journal Article | Journal: Clinical biochemistry | Year: 2014

The purpose of this study was to identify the mutations in the glutaryl-CoA dehydrogenase gene (GCDH) in ten Cypriot patients with Glutaric aciduria type I (GAI).Molecular analysis of the GCDH gene was performed by direct sequencing of the patients genomic DNA. In silico tools were applied to predict the effect of the novel variants on the structure and function of the protein.All disease alleles were characterized (mutation detection rate 100%). Five missense mutations were identified: c.192G>T (p.Glu64Asp) and c.803G>T (p.Gly268Val), which are novel, and three previously described mutations, c.1123T>C (p.Cys375Arg), c.1204C>T (p.Arg402Trp) and c.1286C>T (p.Thr429Met).Two novel mutations, p.Glu64Asp and p.Gly268Val, account for the majority of disease alleles (76.5%) in Cypriot patients with Glutaric aciduria type I. A founder effect for the p.Glu64Asp and the p.Gly268Val can be suggested based on the place of origin of the carriers of these mutations. Identification of the causative mutations of GAI in Cypriot patients will facilitate carrier detection as well as post- and pre-natal diagnosis.


Kousoulidou L.,Cyprus Institute of Neurology and Genetics | Moutafi M.,Cyprus Institute of Neurology and Genetics | Nicolaides P.,Cyprus Paediatric Neurology Institute | Hadjiloizou S.,Cyprus Paediatric Neurology Institute | And 5 more authors.
BioMed Research International | Year: 2013

Autism spectrum disorders (ASDs) comprise a distinct entity of neurodevelopmental disorders with a strong genetic component. Despite the identification of several candidate genes and causative genomic copy number variations (CNVs), the majority of ASD cases still remain unresolved. We have applied microarray-based comparative genomic hybridization (array-CGH) using Agilent 400K custom array in the first Cyprus population screening for identification of ASD-associated CNVs. A cohort of 50 ASD patients (G1), their parents (G2), 50 ethnically matched normal controls (G3), and 80 normal individuals having children with various developmental and neurological conditions (G4) were tested. As a result, 14 patients were found to carry 20 potentially causative aberrations, two of which were de novo. Comparison of the four population groups revealed an increased rate of rare disease-associated variants in normal parents of children with autism. The above data provided additional evidence, supporting the complexity of ASD aetiology in comparison to other developmental disorders involving cognitive impairment. Furthermore, we have demonstrated the rationale of a more targeted approach combining accurate clinical description with high-resolution population-oriented genomic screening for defining the role of CNVs in autism and identifying meaningful associations on the molecular level. © 2013 Ludmila Kousoulidou et al.


Papathanasiou E.S.,Cyprus Institute of Neurology and Genetics | Lemesiou A.,Cyprus Institute of Neurology and Genetics | Hadjiloizou S.,Cyprus Paediatric Neurology Institute | Myrianthopoulou P.,Cyprus Institute of Neurology and Genetics | And 2 more authors.
Otology and Neurotology | Year: 2010

Introduction: Neurogenic vestibular evoked potentials that are recorded from the scalp have so far been recorded in the form of N3 (click air-conducted), N5 (tone air-conducted), and P10 (bone-conducted stimulus) waveforms. The purpose of this study is to find other vestibular waveforms obtained with air-conducted sound. Methods: The experiments were organized into 4 parts: 1) topographic scalp mapping; 2) determining the consistency in appearance of candidate vestibular waveforms; 3) further characteristics such as their relationship to vestibular evoked myogenic potentials, sensitivity to 5-kHz tone, and threshold of activation; and (D) recording of the new vestibular waveforms in a case of hearing loss. Results: A montage was discovered, O2-P3 and O1-P4 with left and right ear stimulation respectively, that yielded a negative wave at 6 milliseconds after stimulus onset and was labeled N6. It is not a vestibular evoked myogenic potential, disappears with 5-kHz tone stimuli, has a high threshold of stimulation, and is present in a case of hearing loss. DISCUSSION: A new vestibular waveform is discovered that probably originates at or near the midbrain based on its latency. Together with the previously mentioned waves, lesions along the vestibular pathway can now be localized further. © 2010, Otology & Neurotology, Inc.

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