Novel mutation in spacer region of POLG associated with ataxia neuropathy spectrum and gastroparesis

Bostan, Alionka; Glibert, Gérald; Dachy, Bernard; Dan, Bernard

doi:10.1016/j.autneu.2012.06.002

Cited by 5 publications

(5 citation statements)

References 10 publications

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“…Gastroparesis with delayed gastric emptying has been particularly reported in patients with nonsyndromic MIDs due to POLG1 mutations [Bostan et al 2012]. These patients additionally present with sensory-ataxic neuropathy, CPEO, and dysarthria [Bostan et al 2012]. Delayed gastric emptying was also reported in MID patients carrying the m.3243A>G mutation [Nohara et al 2006].…”

Section: Resultsmentioning

confidence: 99%

“…Among the syndromic MIDs, a grossly dilated stomach has been most often reported in MNGIE patients. [Chapman et al 2014] and gastroparesis in SANDO [Bostan et al 2012]. Intractable gastroparesis may be also a phenotypic feature of pyruvate-dehydrogenase deficiency [Tatekawa and Komuro, 2010].…”

Section: Resultsmentioning

confidence: 99%

“…Gastroparesis results in gastric dysmotility with delayed gastric emptying and dilation of the stomach. Gastroparesis with delayed gastric emptying has been particularly reported in patients with nonsyndromic MIDs due to POLG1 mutations [Bostan et al 2012]. These patients additionally present with sensory-ataxic neuropathy, CPEO, and dysarthria [Bostan et al 2012].…”

Section: Abnormalities Of Gastrointestinal Hollow Organsmentioning

confidence: 99%

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Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Finsterer

Frank

2016

Therap Adv Gastroenterol

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Mitochondrial disorders (MIDs) due to respiratory-chain defects or nonrespiratory chain defects are usually multisystem conditions [mitochondrial multiorgan disorder syndrome (MIMODS)] affecting the central nervous system (CNS), peripheral nervous system, eyes, ears, endocrine organs, heart, kidneys, bone marrow, lungs, arteries, and also the intestinal tract. Frequent gastrointestinal (GI) manifestations of MIDs include poor appetite, gastroesophageal sphincter dysfunction, constipation, dysphagia, vomiting, gastroparesis, GI pseudo-obstruction, diarrhea, or pancreatitis and hepatopathy. Rare GI manifestations of MIDs include dry mouth, paradontosis, tracheoesophageal fistula, stenosis of the duodeno-jejunal junction, atresia or imperforate anus, liver cysts, pancreas lipomatosis, pancreatic cysts, congenital stenosis or obstruction of the GI tract, recurrent bowel perforations with intra-abdominal abscesses, postprandial abdominal pain, diverticulosis, or pneumatosis coli. Diagnosing GI involvement in MIDs is not at variance from diagnosing GI disorders due to other causes. Treatment of mitochondrial GI disease includes noninvasive or invasive measures. Therapy is usually symptomatic. Only for myo-neuro-gastro-intestinal encephalopathy is a causal therapy with autologous stem-cell transplantation available. It is concluded that GI manifestations of MIDs are more widespread than so far anticipated and that they must be recognized as early as possible to initiate appropriate diagnostic work-up and avoid any mitochondrion-toxic treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Abnormalities Of Gastrointestinal Hollow Organsmentioning

confidence: 99%

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Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Finsterer

Frank

2016

Therap Adv Gastroenterol

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“…A different missense substitution at the same position caused the same amino acid change (p.Q308H), which has been identified in a patient with arPEO disorder (Horvath et al, 2006). Different amino acid changes at the same codons (c.915C>G/ S305R, c.1970G>A/p.R597W, c.2246T>C/F749S) have been observed in individuals with features suggestive of POLG deficiency (Bostan et al, 2012;Nesbitt et al, 2014;Qian et al, 2015;Saneto et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions

Hou

Zhao

Xie

et al. 2022

Molec Gen & Gen Med

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Objectives This study aimed to investigate the clinical and genetic spectrum in Chinese patients with multiple mtDNA deletions presenting with autosomal‐inherited mitochondrial progressive external ophthalmoplegia (PEO). Methods Long‐range polymerase chain reaction and massively parallel sequencing of the mitochondrial genome were performed to detect deletions in muscle mtDNA of 274 unrelated families. Then, targeted next generation sequencing was used to detect nuclear gene variations in patients with multiple mtDNA deletions. Results A total of 40 Chinese PEO patients (10 males and 30 females) from 20 families were found to have multiple mtDNA deletions in this study, and the median age at onset was 35 (1–70) years. PEO and positive family history were the two prominent features of these patients, and ataxia, neuropathy, and hypogonadism were also present as onset symptoms in some patients. Fifteen of 20 probands with multiple mtDNA deletions were identified to carry nuclear gene variants; eight (40.0%) probands had variants within POLG , two (10.0%) within TWNK , two (10.0%) within RRM2B , two (10.0%) within TK2 , and one (5.0%) within POLG2 . A total of 24 variants were found in these five nuclear genes, of which 19 were novel. The causal nuclear genetic factors in five pedigrees remain undetermined. Conclusions The POLG gene is the most common disease‐causing gene in this group of PEO patients with multiple mtDNA deletions. While inherited PEO is the most prominent symptoms in these patients, genotypic and phenotypic heterogeneity still exist, for example in onset age, initial symptoms, and accompanying manifestations.

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“…60 Progressive external ophthalmoplegia was a phenotypic feature in a patient with mitochondrial neurogastrointestinal encephalomyopathy, 8 Wolfram syndrome, 54 Leigh syndrome, autosomal dominant optic atrophy, and mitochondrial recessive ataxia syndrome. 61 Progressive external ophthalmoplegia has been also described in MERRF syndrome. 62 Infantile-onset spinocerebellar ataxia is a Finnish disease, and some of the 24 cases reported so far developed ophthalmoplegia.…”

Section: Secondary Ophthalmologic Mitochondrial Disorder Manifestationsmentioning

confidence: 99%

The Eye on Mitochondrial Disorders

2015

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Ophthalmologic manifestations of mitochondrial disorders are frequently neglected or overlooked because they are often not regarded as part of the phenotype. This review aims at summarizing and discussing the etiology, pathogenesis, diagnosis, and treatment of ophthalmologic manifestations of mitochondrial disorders. Review of publications about ophthalmologic involvement in mitochondrial disorders by search of Medline applying appropriate search terms. The eye is frequently affected by syndromic as well as nonsyndromic mitochondrial disorders. Primary and secondary ophthalmologic manifestations can be differentiated. The most frequent ophthalmologic manifestations of mitochondrial disorders include ptosis, progressive external ophthalmoplegia, optic atrophy, retinopathy, and cataract. More rarely occurring are nystagmus and abnormalities of the cornea, ciliary body, intraocular pressure, the choroidea, or the brain secondarily affecting the eyes. It is important to recognize and diagnose ophthalmologic manifestations of mitochondrial disorders as early as possible because most are accessible to symptomatic treatment with partial or complete short-term or long-term beneficial effect. Ophthalmologic manifestations of mitochondrial disorders need to be appropriately diagnosed to initiate the most effective management and guarantee optimal outcome.

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Novel mutation in spacer region of POLG associated with ataxia neuropathy spectrum and gastroparesis

Cited by 5 publications

References 10 publications

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Gastrointestinal manifestations of mitochondrial disorders: a systematic review

Novel and recurrent nuclear gene variations in a cohort of Chinese progressive external ophthalmoplegia patients with multiple mtDNA deletions

The Eye on Mitochondrial Disorders

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