title: Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome.
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.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Services de Génétique, de Cytogénétique et de Maladies Métaboliques, Hôpital Necker-Enfants Malades, 149, rue de Sèvres 75743 Paris cedex 15, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Haudry
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Valerie
authors.initials: V
authors.lastname: Malan
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.forename: Zahra
authors.initials: Z
authors.lastname: Assouline
authors.forename: Solenn
authors.initials: S
authors.lastname: Pruvost
authors.forename: Anais
authors.initials: A
authors.lastname: Brassier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Agnès
authors.initials: A
authors.lastname: Rötig
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Lebre
mesh_terms: D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2; D055028:Comparative Genomic Hybridization; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D018895:Microsatellite Repeats; D017240:Mitochondrial Myopathies / Q000235:genetics*; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*; D013577:Syndrome; D024182:Uniparental Disomy; D028361:Mitochondrial Diseases
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase