Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome.
Mol Genet Metab
; 107(4): 700-4, 2012 Dec.
Article
em En
| MEDLINE
| ID: mdl-23141463
ABSTRACT
We report maternal uniparental disomy of chromosome 2 (matUPD2) in a 9-month-old girl presenting with hepatocerebral mitochondrial DNA depletion syndrome. This patient was homozygous for the c.352C>T (p.Arg118Cys) mutation in DGUOK gene. The proband's mother was heterozygous for the mutation was absent in DNA of the father. For proband, the absence of paternal contribution at the DGUOK locus prompted us to exclude intragenic DGUOK deletion of the paternal allele with Multiplex ligation-dependent probe amplification (MLPA) analysis. We also excluded non-paternity by studying various markers at different loci. Then we performed an analysis of copy number variations and absence of heterozygosity (AOH) on the proband DNA using high resolution oligonucleotides microarray. Several large regions of AOH with no copy number change were detected on chromosome 2 and one of these AOH regions encompassed DGUOK gene. These results were confirmed with haplotype analysis using polymorphic markers. Informative SNPs and microsatellites markers spanning the whole chromosome 2 showed a matUPD2 with heterodisomy and isodisomy regions, the absence of paternal allele and presence of two maternal alleles, with only one maternal allele on the region of DGUOK locus in 2p13.1. This is the first demonstration of matUPD2 with segmental isodisomy at 2p13.1 locus in hepatocerebral mitochondrial DNA depletion syndrome. The identification of UPD2 will impact genetic counseling for the proband's parents. Because the recurrence risk for UPD2 is very low, the risk for disease in further offspring for this couple is negligible.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Miopatias Mitocondriais
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Fosfotransferases (Aceptor do Grupo Álcool)
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Dissomia Uniparental
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Mutação
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
/
Humans
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Infant
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
França