Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings

Prasad, Chitra; Mélancon, Serge B.; Rupar, C. Anthony; Prasad, Asuri N.; Nunez, Laura Dempsey; Rosenblatt, David S.; Majewski, Jacek

doi:10.1016/j.ymgme.2012.12.007

Cited by 22 publications

(14 citation statements)

References 26 publications

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“…In an infant with MDS, but without detection of the underlying genetic defect, RTA developed 1 year after liver transplantation and was attributed to tacrolimus toxicity and renal involvement in the MID (37). In three siblings with MDS due to a C10orf2 (twinkle) mutation, the MDS manifested as hepatocerebral syndrome and as proximal renal tubulopathy (Table III) (38). Renal tubulopathy was also reported in a female newborn with MDS carrying an mtDNA copy number of only 2% (39).…”

Section: Mdsmentioning

confidence: 97%

Renal manifestations of primary mitochondrial disorders

Finsterer

Scorza

2017

Biomedical Reports

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Section: Mdsmentioning

confidence: 97%

Renal manifestations of primary mitochondrial disorders

Finsterer

Scorza

2017

Biomedical Reports

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“…The majority of individuals presenting with these syndromes do not have a renal phenotype; however, a few individuals with a kidney phenotype have been identified with an mtDNA-depletion syndrome related to several genes ( Table 2). The renal phenotype is most characteristic of renal tubular dysfunction, [72][73][74][75][76][77][78] but renal failure has also been described. 79 …”

Section: Mitochondrial Dna-depletion Syndromesmentioning

confidence: 99%

Renal manifestations of genetic mitochondrial disease

O’Toole¹

2014

IJNRD

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Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant variability in their clinical presentation and the broad spectrum of genes implicated in their etiology. These features contribute to the challenges of establishing a definitive diagnosis and understanding the pathogenetic mechanisms leading to kidney involvement in these diseases. Here, we review the deoxyribonucleic acid variants in the mitochondrial and nuclear genomes that have been associated with a kidney phenotype, and examine some of the possible pathogenic mechanisms that may contribute to the expression of a renal phenotype.

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“…Only ten patients have been previously reported with MDS caused by autosomal recessive Twinkle mutations, with survival ranging from three months to 4.5 years (Table). [4][5][6][7][8] Commonly reported clinical features of failure to thrive, severe hypotonia, seizures, and abnormal eye movements were represented in our patient. Dyskinesias 5,8 and ataxia 5 have been reported in a subset of patients.…”

Section: Discussionmentioning

confidence: 55%

“…8 Renal tubulopathy has been reported in four patients, including ours. 6,7 In previously reported patients, MRI findings ranged from normal to cerebellar atrophy. In our patient, mild cortical atrophy was present by four months.…”

Section: Discussionmentioning

confidence: 98%

Twinkle-Associated Mitochondrial DNA Depletion

Remtulla

Nguyen

Prasad

et al. 2019

Pediatric Neurology

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BACKGROUND: Autosomal recessive mutations in the nuclear Twinkle (C10orf2) gene cause a mitochondrial DNA depletion syndrome (MDS) characterized by early onset hepatoencephalopathy. METHODS: We report a severe, early onset encephalopathy and multisystem failure case caused by novel recessive Twinkle gene mutations. Patient clinical, laboratory, and pathological features are reported and Twinkle-associated MDS literature reviewed. RESULTS: Typical presentation includes symptom onset before age six months, failure to thrive, psychomotor regression, epileptic encephalopathy, sensory axonal neuropathy, cholestatic liver dysfunction, and occasionally, renal tubulopathy, movement disorders, and ophthalmoplegia. Death is typical before age four years. CONCLUSIONS: In the differential diagnosis of early onset encephalopathy and multisystem failure, MDS should be considered.

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Exome sequencing reveals a homozygous mutation in TWINKLE as the cause of multisystemic failure including renal tubulopathy in three siblings

Cited by 22 publications

References 26 publications

Renal manifestations of primary mitochondrial disorders

Renal manifestations of primary mitochondrial disorders

Renal manifestations of genetic mitochondrial disease

Twinkle-Associated Mitochondrial DNA Depletion

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