Uniparental disomy (UPD) other than 15: Phenotypes and bibliography updated

Kotzot, Dieter; Utermann, Gerd

doi:10.1002/ajmg.a.30483

Cited by 145 publications

(125 citation statements)

References 198 publications

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“…Prevailing evidence does not support the existence of imprinted loci on either of those chromosomes. 23,24 Consistent with these findings, the two patients described here have clinical findings typical of MDS without any obvious additional findings that may be attributed to the underlying isodisomy.…”

Section: Discussionsupporting

confidence: 84%

Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis

et al. 2011

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Mitochondrial DNA (mtDNA) depletion syndrome encompasses a heterogeneous group of disorders characterized by a reduction in the mtDNA copy number. We identified two patients with clinical presentations consistent with mtDNA depletion syndrome (MDS), who were subsequently found to have apparently homozygous point mutations in TYMP and DGUOK, two of the nine nuclear genes commonly associated with these disorders. Further sequence analyses of parents indicated that in each case only one parent; the mother of the first and the father of the second, was a heterozygous carrier of the mutation identified in the affected child. The presence of underlying deletions was ruled out by use of a custom target array comparative genomic hybridization (CGH) platform. A high-density single-nucleotide polymorphism (SNP) array analysis revealed that the first patient had a region of copy-neutral absence of heterozygosity (AOH) consistent with segmental isodisomy for an 11.3 Mb region at the long-arm terminus of chromosome 22 (including the TYMP gene), and the second patient had results consistent with complete isodisomy of chromosome 2 (where the DGUOK gene is located). The combined sequencing, array CGH and SNP array approaches have demonstrated the first cases of MDS due to uniparental isodisomy. This diagnostic scenario also demonstrates the necessity of comprehensive examination of the underlying molecular defects of an apparently homozygous mutation in order to provide patients and their families with the most accurate molecular diagnosis and genetic counseling.

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Section: Discussionsupporting

confidence: 84%

Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis

et al. 2011

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“…Paternal isodisomy for chromosome 2 has been described before in the context of Crigler-Najjar syndrome (Petit, et al, 2005) steroid 5 alpha reductase 2 deficiency and retinal dystrophy (Kotzot and Utermann, 2005). Similarly, maternal uniparental disomy of chromosome 2 may result in trifunctional protein deficiency.…”

Section: Patient Ethnicity Sexmentioning

confidence: 80%

Clinical and molecular features of mitochondrial DNA depletion due to mutations in deoxyguanosine kinase

Dimmock¹,

Zhang²,

et al. 2008

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Published mutations in deoxyguanosine kinase (DGUOK) cause mitochondrial DNA depletion and a clinical phenotype that consists of neonatal liver failure, nystagmus and hypotonia. In this series, we have identified 15 different mutations in the DGUOK gene from 9 kindreds. Among them, 12 have not previously been reported. Nonsense, splice site, or frame-shift mutations that produce truncated proteins predominate over missense mutations. All patients who harbor null mutations had early onset liver failure and significant neurological disease. These patients have all died before 2-years of age. Conversely, two patients carrying missense mutations had isolated liver disease and are alive in their 4th year of life without liver transplant. Five subjects were detected by newborn screening, with elevated tyrosine or phenylalanine. Consequently, this disease should be considered if elevated tyrosine is identified by newborn screening. Mitochondrial DNA content was below 10% of controls in liver in all but one case and modestly reduced in blood cells. With this paper a total of 39 different mutations in DGUOK have been identified. The most frequent mutation, c.763_c.766dupGATT, occurs in 8 unrelated kindreds. 70% of mutations occur in only one kindred, suggesting full sequencing of this gene is required for diagnosis. The presentation of one case with apparent viral hepatitis, without neurological disease, suggests that this disease should be considered in patients with infantile liver failure regardless of the presence of neurological features or apparent infectious etiology.

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“…In female carriers, the empiric risk of having a child with an unbalanced translocation is about 10%, and in males it is only 1-2% (Ferguson-Smith, 1983;Daniel et al, 1989). In both sexes, the translocations rob(14q21q) and rob(15q21q) harbour the additional risk of uniparental disomy 14 or 15 as a consequence of trisomic rescue (Kotzot and Utermann, 2005) which is associated with specific clinical syndromes.…”

Section: Carriers Of a Balanced Heterologous Robertsonian Translocationmentioning

confidence: 99%

“…Due to the frequency of trisomy 21, UPD of this chromosome should be a well-known aberration. Indeed, maternal as well as paternal UPD21 (upd(21)mat, upd(21)pat) have been reported for several times (for review: Kotzot and Utermann, 2005), including healthy carriers. Based on the latter finding, it can be decided that the clinical course of upd(21)mat or upd(21)pat carriers is rather caused by a hidden chromosomal mosaicism which can be delineated from the UPD formation mechanism or by homozygosity of a recessive allele than by the UPD itself.…”

Section: Ds and Uniparental Disomymentioning

confidence: 99%