Novel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome.

Hdl Handle:
http://hdl.handle.net/10147/189990
Title:
Novel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome.
Authors:
Walsh, David J; Sills, Eric S; Lambert, Deborah M; Gregersen, Nils; Malone, Fergal D; Walsh, Anthony P H
Affiliation:
The Sims Institute/Sims International Fertility Clinic, Dublin 14, Ireland.
Citation:
Novel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome., 3 (2):223-6 Mol Med Report
Journal:
Molecular medicine reports
Issue Date:
Mar-2010
URI:
http://hdl.handle.net/10147/189990
DOI:
10.3892/mmr_00000243
PubMed ID:
21472225
Additional Links:
http://www.spandidos-publications.com/mmr/3/2/223
Abstract:
Ethylmalonic encephalopathy (EE) is an autosomally recessive inherited disorder with a relentlessly progressive decline in neurological function, usually fatal by the age of ten. It is characterised by generalised hypotonia, psychomotor regression, spastic tetraparesis, dystonia, seizures and, eventually, global neurological failure. Approximately 50 reports have been published worldwide describing this devastating disease, most involving patients of Mediterranean or Arab origin. The fundamental defect in EE likely involves the impairment of a mitochondrial sulphur dioxygenase coded by the ETHE1 gene responsible for the catabolism of sulphide, which subsequently accumulates to toxic levels. A diagnosis of EE should initiate careful genetic evaluation and counselling, particularly if the parents intend to have additional offspring. The present report describes the diagnosis of EE in a reproductive endocrinology context, where both members of a non-consanguineous couple were confirmed to be carriers of an identical A↷G mutation. This previously unknown mutation at nucleotide position c.494 resulted in an amino acid substitution, p.Asp165Gly. Although consideration was given to in vitro fertilisation, embryo biopsy and single gene pre-implantation genetic diagnosis, the couple decided to first utilise a less aggressive therapeutic approach with donor sperm insemination. Pregnancy with a low risk of EE was indeed achieved; however, the infant was affected with a different anomaly (hypoplastic left heart). As this case demonstrates, prior to the initiation of fertility therapy, genetic analysis may be used to provide a confirmatory diagnosis when EE is suspected.
Item Type:
Article
Language:
en
Description:
Ethylmalonic encephalopathy (EE) is an autosomally recessive inherited disorder with a relentlessly progressive decline in neurological function, usually fatal by the age of ten. It is characterised by generalised hypotonia, psychomotor regression, spastic tetraparesis, dystonia, seizures and, eventually, global neurological failure. Approximately 50 reports have been published worldwide describing this devastating disease, most involving patients of Mediterranean or Arab origin. The fundamental defect in EE likely involves the impairment of a mitochondrial sulphur dioxygenase coded by the ETHE1 gene responsible for the catabolism of sulphide, which subsequently accumulates to toxic levels. A diagnosis of EE should initiate careful genetic evaluation and counselling, particularly if the parents intend to have additional offspring. The present report describes the diagnosis of EE in a reproductive endocrinology context, where both members of a non-consanguineous couple were confirmed to be carriers of an identical A↷G mutation. This previously unknown mutation at nucleotide position c.494 resulted in an amino acid substitution, p.Asp165Gly. Although consideration was given to in vitro fertilisation, embryo biopsy and single gene pre-implantation genetic diagnosis, the couple decided to first utilise a less aggressive therapeutic approach with donor sperm insemination. Pregnancy with a low risk of EE was indeed achieved; however, the infant was affected with a different anomaly (hypoplastic left heart). As this case demonstrates, prior to the initiation of fertility therapy, genetic analysis may be used to provide a confirmatory diagnosis when EE is suspected.
ISSN:
1791-3004

Full metadata record

DC FieldValue Language
dc.contributor.authorWalsh, David Jen
dc.contributor.authorSills, Eric Sen
dc.contributor.authorLambert, Deborah Men
dc.contributor.authorGregersen, Nilsen
dc.contributor.authorMalone, Fergal Den
dc.contributor.authorWalsh, Anthony P Hen
dc.date.accessioned2011-11-18T15:23:53Z-
dc.date.available2011-11-18T15:23:53Z-
dc.date.issued2010-03-
dc.identifier.citationNovel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome., 3 (2):223-6 Mol Med Reporten
dc.identifier.issn1791-3004-
dc.identifier.pmid21472225-
dc.identifier.doi10.3892/mmr_00000243-
dc.identifier.urihttp://hdl.handle.net/10147/189990-
dc.descriptionEthylmalonic encephalopathy (EE) is an autosomally recessive inherited disorder with a relentlessly progressive decline in neurological function, usually fatal by the age of ten. It is characterised by generalised hypotonia, psychomotor regression, spastic tetraparesis, dystonia, seizures and, eventually, global neurological failure. Approximately 50 reports have been published worldwide describing this devastating disease, most involving patients of Mediterranean or Arab origin. The fundamental defect in EE likely involves the impairment of a mitochondrial sulphur dioxygenase coded by the ETHE1 gene responsible for the catabolism of sulphide, which subsequently accumulates to toxic levels. A diagnosis of EE should initiate careful genetic evaluation and counselling, particularly if the parents intend to have additional offspring. The present report describes the diagnosis of EE in a reproductive endocrinology context, where both members of a non-consanguineous couple were confirmed to be carriers of an identical A↷G mutation. This previously unknown mutation at nucleotide position c.494 resulted in an amino acid substitution, p.Asp165Gly. Although consideration was given to in vitro fertilisation, embryo biopsy and single gene pre-implantation genetic diagnosis, the couple decided to first utilise a less aggressive therapeutic approach with donor sperm insemination. Pregnancy with a low risk of EE was indeed achieved; however, the infant was affected with a different anomaly (hypoplastic left heart). As this case demonstrates, prior to the initiation of fertility therapy, genetic analysis may be used to provide a confirmatory diagnosis when EE is suspected.en
dc.description.abstractEthylmalonic encephalopathy (EE) is an autosomally recessive inherited disorder with a relentlessly progressive decline in neurological function, usually fatal by the age of ten. It is characterised by generalised hypotonia, psychomotor regression, spastic tetraparesis, dystonia, seizures and, eventually, global neurological failure. Approximately 50 reports have been published worldwide describing this devastating disease, most involving patients of Mediterranean or Arab origin. The fundamental defect in EE likely involves the impairment of a mitochondrial sulphur dioxygenase coded by the ETHE1 gene responsible for the catabolism of sulphide, which subsequently accumulates to toxic levels. A diagnosis of EE should initiate careful genetic evaluation and counselling, particularly if the parents intend to have additional offspring. The present report describes the diagnosis of EE in a reproductive endocrinology context, where both members of a non-consanguineous couple were confirmed to be carriers of an identical A↷G mutation. This previously unknown mutation at nucleotide position c.494 resulted in an amino acid substitution, p.Asp165Gly. Although consideration was given to in vitro fertilisation, embryo biopsy and single gene pre-implantation genetic diagnosis, the couple decided to first utilise a less aggressive therapeutic approach with donor sperm insemination. Pregnancy with a low risk of EE was indeed achieved; however, the infant was affected with a different anomaly (hypoplastic left heart). As this case demonstrates, prior to the initiation of fertility therapy, genetic analysis may be used to provide a confirmatory diagnosis when EE is suspected.-
dc.language.isoenen
dc.relation.urlhttp://www.spandidos-publications.com/mmr/3/2/223en
dc.titleNovel ETHE1 mutation in a carrier couple having prior offspring affected with ethylmalonic encephalopathy: Genetic analysis, clinical management and reproductive outcome.en
dc.typeArticleen
dc.contributor.departmentThe Sims Institute/Sims International Fertility Clinic, Dublin 14, Ireland.en
dc.identifier.journalMolecular medicine reportsen
dc.description.provinceLeinster-

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