Novel mutation in <i>DGUOK</i> in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria

Tadiboyina, Venu T.; Rupar, Anthony; Atkison, Paul; Feigenbaum, Annette; Kronick, Jonathan B.; Wang, Jian; Hegele, Robert A.

doi:10.1002/ajmg.a.30748

Cited by 42 publications

(45 citation statements)

References 24 publications

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“…The hepatocerebral form is characterized by an onset before 6 months of age, early progressive liver failure, muscle hypotonia, hyperreflexia, and irritability. Death is usually by 12 months of age due to liver failure [Tadiboyina et al, 2005]. Three Old Colony Mennonite MDS patients from two unrelated families living in Southern Ontario were reported to be homozygous for a novel c.763G > T mutation in exon 6 of deoxyguanosine kinase (DGUOK).…”

Section: Methodsmentioning

confidence: 99%

Unique disease heritage of the Dutch‐German Mennonite population

Orton

Innes

Chudley

et al. 2008

American J of Med Genetics Pt A

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The Dutch-German Mennonites are a religious isolate with foundational roots in the 16th century. A tradition of endogamy, large families, detailed genealogical records, and a unique disease history all contribute to making this a valuable population for genetic studies. Such studies in the Dutch-German Mennonite population have already contributed to the identification of the causative genes in several conditions such as the incomplete form of X-linked congenital stationary night blindness (CSNB2; previously iCSNB) and hypophosphatasia (HOPS), as well as the discovery of founder mutations within established disease genes (MYBPC1, CYP17alpha). The Dutch-German Mennonite population provides a strong resource for gene discovery and could lead to the identification of additional disease genes with relevance to the general population. In addition, further research developments should enhance delivery of clinical genetic services to this unique community. In the current review we discuss 31 genetic conditions, including 17 with identified gene mutations, within the Dutch-German Mennonite population.

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Section: Methodsmentioning

confidence: 99%

Unique disease heritage of the Dutch‐German Mennonite population

Orton

Innes

Chudley

et al. 2008

American J of Med Genetics Pt A

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“…This appears to be a rare phenotype in the literature. However, the large series published to date (Ferrari, et al, 2005;Freisinger, et al, 2006;Taanman, et al, 2002;Tadiboyina, et al, 2005) and our own series are limited by study selection criteria or referral patterns that ascertain subjects with multisystem disease or a hepatocerebral phenotype. Further investigation is warranted to explore the role of DGUOK mutations, and perhaps other genes associated with mtDNA depletion, in isolated liver failure.…”

Section: Patient Ethnicity Sexmentioning

confidence: 99%

“…We have found this mutation in several control chromosomes in a heterozygous state. References: Freisinger (Freisinger, et al, 2006) Labarthe (Labarthe, et al, 2005) Mancuso a (Mancuso, et al, 2003) Mancuso b (Mancuso, et al, 2005) Mandel Mousson (Mousson de Camaret, et al, 2007) Salviati (Salviati, et al, 2002) Sarzi, Slama (Slama, et al, 2005a) Taanman (Taanman, et al, 2002) Tadiboyina (Tadiboyina, et al, 2005) Wang …”

Section: Patient Ethnicity Sexmentioning

confidence: 99%

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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“…A minority of affected individuals present initially in infancy or childhood with isolated hepatic disease, occasionally following a viral illness. Affected individuals with this form may develop mild hypotonia and renal involvement manifesting as proteinuria and aminoaciduria [2,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55]. More recently, DGUOK mutations have been reported in a neonate with clinical and autopsy findings consistent with neonatal hemochromatosis and mtDNA depletion [56], and in individuals with adult-onset mitochondrial myopathy and mtDNA multiple deletions in skeletal muscle [57].…”

Section: Dguok-related Hepatocerebral Mdsmentioning

confidence: 99%

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

2013

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Mitochondrial DNA (mtDNA) depletion syndromes (MDS) are a genetically and clinically heterogeneous group of autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs. MDS are due to defects in mtDNA maintenance caused by mutations in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2,

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Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria

Cited by 42 publications

References 24 publications

Unique disease heritage of the Dutch‐German Mennonite population

Unique disease heritage of the Dutch‐German Mennonite population

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

Mitochondrial DNA Depletion Syndromes: Review and Updates of Genetic Basis, Manifestations, and Therapeutic Options

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