title: The first family with Tay-Sachs disease in Cyprus: Genetic analysis reveals a nonsense (c.78G>A) and a silent (c.1305C>T) mutation and allows preimplantation genetic diagnosis.
abstract: 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 silent mutation 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.
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Georgiou
authors.affiliation: Department of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: George
authors.initials: G
authors.lastname: Christopoulos
authors.affiliation: Department of Clinical Genetics, Archbishop Makarios III Hospital and The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.
authors.forename: Violetta
authors.initials: V
authors.lastname: Anastasiadou
authors.affiliation: Cyprus Paediatric Neurology Institute, Nicosia, Cyprus.
authors.forename: Stavros
authors.initials: S
authors.lastname: Hadjiloizou
authors.affiliation: Department of Biochemical Genetics, Guy's Hospital, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Cregeen
authors.affiliation: Department of Biochemical Genetics, Guy's Hospital, London, UK.
authors.forename: Marie
authors.initials: M
authors.lastname: Jackson
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Gavriella
authors.initials: G
authors.lastname: Mavrikiou
authors.affiliation: Department of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Marina
authors.initials: M
authors.lastname: Kleanthous
authors.affiliation: Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
authors.forename: Anthi
authors.initials: A
authors.lastname: Drousiotou
keywords: ADO, Allele Dropout; CVS, Chorionic Villus Sampling; Cyprus; EEG, Electroencephalogram; GM2 gangliosidosis; Juvenile Tay-Sachs disease; MLPA, Multiplex Ligation Dependent Probe Amplification; MRI, Magnetic Resonance Imaging; PCR, Polymerase Chain Reaction; PGD, Preimplantation Genetic Diagnosis; Preimplantation genetic diagnosis; STR, Short Tandem Repeat; Silent mutation; TSD, Tay-Sachs disease; β-Hexosaminidase A