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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

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 juveni...

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Autores principales: Georgiou, Theodoros, Christopoulos, George, Anastasiadou, Violetta, Hadjiloizou, Stavros, Cregeen, David, Jackson, Marie, Mavrikiou, Gavriella, Kleanthous, Marina, Drousiotou, Anthi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287815/
https://www.ncbi.nlm.nih.gov/pubmed/25606403
http://dx.doi.org/10.1016/j.mgene.2014.01.007
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author Georgiou, Theodoros
Christopoulos, George
Anastasiadou, Violetta
Hadjiloizou, Stavros
Cregeen, David
Jackson, Marie
Mavrikiou, Gavriella
Kleanthous, Marina
Drousiotou, Anthi
author_facet Georgiou, Theodoros
Christopoulos, George
Anastasiadou, Violetta
Hadjiloizou, Stavros
Cregeen, David
Jackson, Marie
Mavrikiou, Gavriella
Kleanthous, Marina
Drousiotou, Anthi
author_sort Georgiou, Theodoros
collection PubMed
description 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.
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spelling pubmed-42878152015-01-20 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 Georgiou, Theodoros Christopoulos, George Anastasiadou, Violetta Hadjiloizou, Stavros Cregeen, David Jackson, Marie Mavrikiou, Gavriella Kleanthous, Marina Drousiotou, Anthi Meta Gene Article 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. Elsevier 2014-02-19 /pmc/articles/PMC4287815/ /pubmed/25606403 http://dx.doi.org/10.1016/j.mgene.2014.01.007 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Georgiou, Theodoros
Christopoulos, George
Anastasiadou, Violetta
Hadjiloizou, Stavros
Cregeen, David
Jackson, Marie
Mavrikiou, Gavriella
Kleanthous, Marina
Drousiotou, Anthi
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
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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287815/
https://www.ncbi.nlm.nih.gov/pubmed/25606403
http://dx.doi.org/10.1016/j.mgene.2014.01.007
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