Emmanouil Athanasakis

Publications (17) View all

• Article: Congenital hyperinsulinism: Clinical and molecular analysis of a large Italian cohort.

  Flavio Faletra, Emmanouil Athanasakis, Anna Morgan, Xevi Biarnés, Federico Fornasier, Rossella Parini, Francesca Furlan, Arianna Boiani, Arianna Maiorana, Carlo Dionisi-Vici, Laura Giordano, Alberto Burlina, Alessandro Ventura, Paolo Gasparini
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  ABSTRACT: Congenital hyperinsulinism (CHI) is a genetic disorder characterized by profound hypoglycaemia related to an inappropriate insulin secretion. It is a heterogeneous disease classified into two major subgroups: "channelopathies" due to defects in ATP-sensitive potassium channel, encoded by ABCC8 and KCNJ11 genes, and "metabolopathies" caused by mutation of several genes (GLUD1, GCK, HADH, SLC16A1, HNF4A and HNF1A) and involved in different metabolic pathways. To elucidate the genetic aetiology of CHI in the Italian population, we conducted an extensive sequencing analysis of the CHI-related genes in a large cohort of 36 patients: Twenty-nine suffering from classic hyperinsulinism (HI) and seven from hyperinsulinism-hyperammonemia (HI/HA). Seventeen mutations have been found in fifteen HI patients and five mutations in five HI/HA patients. Our data confirm the major role of ATP-sensitive potassium channel in the pathogenesis of Italian cases (~70%) while the remaining percentage should be attributed to other. A better knowledge of molecular basis of CHI would lead to improve strategies for genetic screening and prenatal diagnosis. Moreover, genetic analysis might also help to distinguish the two histopathological forms of CHI, which would lead to a clear improvement in the treatment and in genetic counseling.
  Gene 03/2013; · 2.34 Impact Factor
• Article: Co-inheritance of two ABCC8 mutations causing an unresponsive congenital hyperinsulinism: Clinical and functional characterization of two novel ABCC8 mutations.

  Flavio Faletra, Kara Snider, Show-Ling Shyng, Irene Bruno, Emmanouil Athanasakis, Paolo Gasparini, Carlo Dionisi-Vici, Alessandro Ventura, Qing Zhou, Charles A Stanley, Alberto Burlina
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  ABSTRACT: Congenital hyperinsulinism (CHI) occurs as a consequence of unregulated insulin secretion from the pancreatic beta-cells. Severe recessive mutations and milder dominant mutations have been described in the ABCC8 and KCNJ11 genes encoding SUR1 and Kir6.2 subunits of the beta-cell ATP-sensitive K(+) channel. Here we report two patients with CHI unresponsive to medical therapy with diazoxide. Sequencing analysis identified a compound heterozygous mutation in ABCC8 in both patients. The first one, is a carrier for the known mild dominant mutation p.Glu1506Lys jointly with the novel mutation p.Glu1323Lys. The second carries the p.Glu1323Lys mutation and a second novel mutation, p.Met1394Arg. Functional studies of both novel alleles showed reduced or null cell surface expression, typical of recessive mutations. Compound heterozygous mutations in congenital hyperinsulinism result in complex interactions. The studying of these mechanisms can improve the knowledge of this disease and modify its therapy.
  Gene 12/2012; · 2.34 Impact Factor
• Article: Genetics of Food Preferences: A First View from Silk Road Populations.

  Nicola Pirastu, Antonietta Robino, Carmela Lanzara, Emmanouil Athanasakis, Laura Esposito, Beverly J Tepper, Paolo Gasparini
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  ABSTRACT: Abstract  Food preferences are the main factor driving food intake and choice. There are good reasons to suspect some genetic influence on food acceptance, not least because genetic factors are implicated in a number of factors that are likely to be related to food choice. In addition, some food dislikes show themselves early in life, before there is any evidence for aversive experiences. Although taste has been widely studied in regards of pure tastes such as bitter or sweet perception, the relationship between taste-related genes and food preferences has seldom been explored. In this work we investigated relationship of 37 taste-related genes with food preferences. The study was carried out during a scientific expedition through Caucasus and Central Asia (Silk Road) analyzing more than 400 samples from 5 different countries. A food preference questionnaire was administered to each participant and a DNA sample was obtained. Other information, such as age, sex, life style and anthropometrical measures, were also collected. We found significant associations with variants of: (1) TAS1R3 gene and liking of Vodka (P= 1.6 × 10(-3) ), white wine (P= 4.0 × 10(-4) ) and lamb meat (P= 1.6 × 10(-3) ); (2) PCLB2 gene and preference for Hot Tea (P= 8.0 × 10(-4) ); (3) TPRV1 gene and beet liking (P= 3.8 × 10(-5) ); and (4) ITPR3 gene and liking of both lamb meat (5.8 × 10(-4) ) and sheep cheese (8.9×10(-4) ). These findings give a new insight on a better understanding, of genetic factors influencing food preferences which is critical to the development of effective dietary interventions, especially for people that may be genetically not predisposed for liking specific nutrients.
  Journal of Food Science 08/2012; · 1.66 Impact Factor
• Source

  Available from: Flavio Faletra

  Article: A Novel CRYBB2 Missense Mutation Causing Congenital Autosomal Dominant Cataract in an Italian Family.

  Flavio Faletra, Adamo Pio d'Adamo, Stefano Pensiero, Emmanouil Athanasakis, Dario Catalano, Irene Bruno, Paolo Gasparini
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  ABSTRACT: Congenital cataract is a leading cause of visual impairment in children and brings approximately 10% of childhood blindness worldwide. Molecular analysis revealed ~60 loci to be associated with several phenotypes of childhood cataracts. Until now, more than 30 loci and 18 genes on different chromosomes have been associated with autosomal dominant congenital cataract (ADCC). Here, we present a three-generation Italian family with a non syndromic ADCC. A linkage analysis carried out using HumanCytoSNP-12 DNA Analysis BeadChip led us to identify ten genomic regions virtually involved in the disease. All the genes located in these regions were scored for possible relationship with ADCC and, according to a strict clinical and genetic selection, 4 genes have been analyzed. A novel sequence variant was found in the CRYBB2 gene (p.Ser143Phe). This variant affects a conserved aminoacid in the third Greek key motif of the protein, cosegregates with the disease phenotype in all affected individuals and is not present both in the unaffected family members and 100 healthy control subjects. Finally, we identified the first CRYBB2 mutation in an Italian family causing a clinical picture of ADCC.
  Ophthalmic Genetics 07/2012; · 0.93 Impact Factor
• Article: Molecular diagnosis of usher syndrome: application of two different next generation sequencing-based procedures.

  Danilo Licastro, Margherita Mutarelli, Ivana Peluso, Kornelia Neveling, Nienke Wieskamp, Rossella Rispoli, Diego Vozzi, Emmanouil Athanasakis, Angela D'Eustacchio, Mariateresa Pizzo, Francesca D'Amico, Carmela Ziviello, Francesca Simonelli, Antonella Fabretto, Hans Scheffer, Paolo Gasparini, Sandro Banfi, Vincenzo Nigro
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  ABSTRACT: Usher syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by visual and hearing impairments. Clinically, it is subdivided into three subclasses with nine genes identified so far. In the present study, we investigated whether the currently available Next Generation Sequencing (NGS) technologies are already suitable for molecular diagnostics of USH. We analyzed a total of 12 patients, most of which were negative for previously described mutations in known USH genes upon primer extension-based microarray genotyping. We enriched the NGS template either by whole exome capture or by Long-PCR of the known USH genes. The main NGS sequencing platforms were used: SOLiD for whole exome sequencing, Illumina (Genome Analyzer II) and Roche 454 (GS FLX) for the Long-PCR sequencing. Long-PCR targeting was more efficient with up to 94% of USH gene regions displaying an overall coverage higher than 25×, whereas whole exome sequencing yielded a similar coverage for only 50% of those regions. Overall this integrated analysis led to the identification of 11 novel sequence variations in USH genes (2 homozygous and 9 heterozygous) out of 18 detected. However, at least two cases were not genetically solved. Our result highlights the current limitations in the diagnostic use of NGS for USH patients. The limit for whole exome sequencing is linked to the need of a strong coverage and to the correct interpretation of sequence variations with a non obvious, pathogenic role, whereas the targeted approach suffers from the high genetic heterogeneity of USH that may be also caused by the presence of additional causative genes yet to be identified.
  PLoS ONE 01/2012; 7(8):e43799. · 4.09 Impact Factor