Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome

Haudry, Coralie; Lonlay, Pascale de; Malan, Valérie; Bôle‐Feysot, Christine; Assouline, Zahra; Pruvost, Solenn; Brassier, Anaïs; Bonnefont, Jean‐Paul; Münnich, Arnold; Rötig, Agnès; Lèbre, Anne-Sophie

doi:10.1016/j.ymgme.2012.10.008

Cited by 16 publications

(13 citation statements)

References 27 publications

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“…Although previous reports have shown that some variants change highly conserved amino acids [ 3 , 4 , 9 , 16 , 20 , 23 ], integrated data show that mutations are not confined to these conserved sites. Many variants occur outside of the conserved region [ 3 – 9 , 11 – 13 , 19 , 21 , 25 , 27 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene

et al. 2017

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The deoxyguanosine kinase (DGUOK) gene controls mitochondrial DNA (mtDNA) maintenance, and variation in the gene can alter or abolish the anabolism of mitochondrial deoxyribonucleotides. A Chinese female infant, whose symptoms included weight stagnation, jaundice, hypoglycemia, coagulation disorders, abnormal liver function, and multiple abnormal signals in the brain, died at about 10 months old. Genetic testing revealed a compound heterozygote of alleles c.128T>C (p.I43T) and c.313C>T (p.R105*) of the DGUOK gene. c.128T>C (p.I43T) is a novel variant located in exon 1 (NM_080916) in the first beta sheet of DGUOK. Her mother was an allele c.313C>T (p.R105*) heterozygote, which is located in DGUOK exon 2 (NM_080916) between the third and fourth alpha helixes. c.313C>T (p.R105*) is predicted to result in a 173 amino acid residue truncation at the C terminus of DGUOK. There are as many as 112 infantile mtDNA depletion syndrome (MDS) cases in the literature related to DGUOK gene variants. These variants include missense mutations, nucleotide deletion, nucleotide insertion, and nucleotide duplication. Integrated data showed that mutations affected both conserved and non-conserved DGUOK amino acids and are associated with patient deaths.

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Section: Discussionmentioning

confidence: 99%

A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene

et al. 2017

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“…Uniparental heterodisomy involves 2 different homologous chromosomes (inherited from both grandparents) from one parent being transmitted to the offspring, indicating a meiosis I error, while uniparental isodisomy involves 2 identical, replica copies of a single homologue of a chromosome, indicating either a meiosis II error or postzygotic chromosomal duplication [Shin et al, 2016]. The phenotypes characteristic of UPD are generally considered to be due to the presence of imprinted genes on the chromosomes involved, as UPD has been associated with trisomy mosaicism or homozygosity of autosomal recessively inherited mutations [Tohyama et al, 2011;Haudry et al, 2012;Hannula-Jouppi et al, 2014]. Imprinting effects likely cause the phenotypic abnormalities characteristic of the distinctive malformation complex observed in patUPD14 syndrome.…”

Section: Discussionmentioning

confidence: 99%

Paternal Uniparental Disomy of Chromosome 14 with Hypospadias

Yuan

Xie

Li³

et al. 2016

Cytogenet Genome Res

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Paternal uniparental disomy 14 (patUPD14) is a distinct, clinically recognizable syndrome. Using a clinical SNP microarray, we identified patUPD14 in a boy with a normal karyotype presenting cardiomyopathy and facial anomalies, a specific configuration of the thoracic ribs (‘coat hanger sign'), and hypospadias. Analyses of polymorphic microsatellites confirmed the diagnosis of patUPD14. We discuss the functions of the genes included in the rearrangement and their involvement in the pathogenesis of these disorders, especially hypospadias. ESR2 single nucleotide polymorphisms (rs944050; 2681-4A>G) have been associated with an increased risk of hypospadias in previous studies. The patient's ESR2 (rs944050) genotype is GG, whereas the parents both exhibit an AG genotype. This report sheds light on the genetic phenomenon in which the combination of a polymorphism and UPD can lead to new phenotypes, such as hypospadias.

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“…2 There was no imprinting gene located on chromosome 2 and both maternal and paternal UPD2 have been reported in individuals with normal phenotypes. 3,4 Considering that there had been no abnormal features, except MDS, we speculated that the homozygous mutation of DGUOK caused by UPD2 was the cause of the disease in this patient. Moreover, to the best of our knowledge, this is the fifth reported case of complete paternal UPD of chromosome 2.…”

Section: To the Editormentioning

confidence: 94%

Mitochondrial DNA depletion syndrome in a newborn with Jaundice Caused by DGUOK mutation and complete uniparental disomy of chromosome 2

Xia

Bai

Zhao

et al. 2020

Pediatrics & Neonatology

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Maternal uniparental disomy of chromosome 2 in a patient with a DGUOK mutation associated with hepatocerebral mitochondrial DNA depletion syndrome

Cited by 16 publications

References 27 publications

A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene

A fatal case of mitochondrial DNA depletion syndrome with novel compound heterozygous variants in the deoxyguanosine kinase gene

Paternal Uniparental Disomy of Chromosome 14 with Hypospadias

Mitochondrial DNA depletion syndrome in a newborn with Jaundice Caused by DGUOK mutation and complete uniparental disomy of chromosome 2

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