Abstract
Uniparental isodisomy arises when an individual inherits two copies of a specific chromosome from a single parent, which can unmask a recessive mutation or cause a problem of genetic imprinting. Here we describe an exceptional case in which the patient simultaneously presents tyrosinemia type 1 and Angelman syndrome. The genetic studies showed that the patient presents paternal uniparental isodisomy of chromosome 15, with absence of the maternal homolog. As a consequence of this isodisomy, the patient is homozygous for the mutation IVS12+5G>A in the FAH gene, located in the chromosomal region 15q23-25, causing tyrosinemia type 1. The mutation was inherited from his father in double dosage, whereas the mother is not a carrier, which implies that the recurrence risk in the family is negligible. On the other hand, the lack of maternal contribution causes Angelman syndrome, a neurodevelopmental disorder associated with a loss of maternal gene expression in chromosome region 15q11-q13, and more specifically, of the UBE3A gene. This gene shows a tissue-specific imprinting, and only the maternally derived allele is expressed in certain areas of the brain. We observed through a literature review that uniparental disomy probably occurs more frequently than suspected, although it is more usually detected when the uniparental disomy implies the appearance of a disease because of the gene imprinting or by reduction to homozygosity of a recessive mutation. The conclusion is that uniparental disomy should always be considered when more than one genetic disease mapping to the same chromosome is present in a patient.
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Abbreviations
- FAH:
-
Fumarylacetoacetate hydrolase
- AS:
-
Angelman syndrome
- UPD:
-
Uniparental disomy
- PCR:
-
Polymerase chain reaction
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Acknowledgements
Ferrer-Bolufer’s work was supported by Fundación para la Investigación del Hospital Universitario La Fe’ and ‘Fundación Bancaja. This work was partially supported by grants PI080648 from the Spanish Ministry of Health (Fondo de Investigacion Sanitaria)/FEDER (Fondo Europeo de DEsarrollo Regional) and ACOMP/2009/216 (Conselleria d’Educació, Generalitat Valenciana).
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Communicated by: K. Michael Gibson
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Angelman syndrome (OMIM 105830)
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Ferrer-Bolufer, I., Dalmau, J., Quiroga, R. et al. Tyrosinemia type 1 and Angelman syndrome due to paternal uniparental isodisomy 15. J Inherit Metab Dis 32 (Suppl 1), 349–353 (2009). https://doi.org/10.1007/s10545-009-9014-9
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DOI: https://doi.org/10.1007/s10545-009-9014-9