Kit Green Sanderson1, Eoghan Millar2, Anupreet Tumber2, Regan Klatt2, Neal Sondheimer1,3, Ajoy Vincent4,5. 1. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada. 2. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada. 3. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada. 4. Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Canada. ajoy.vincent@sickkids.ca. 5. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, University of Toronto, Toronto, Canada. ajoy.vincent@sickkids.ca.
Abstract
OBJECTIVE: To report the clinical and novel electrophysiological features in a child with POLG-related sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). METHODS: The proband, a male child of Indian descent, underwent serial systemic and ophthalmological evaluations from birth until 14 years of age. Eye examinations included visual acuity and extraocular movement assessments, fundus photography, spectral domain optical coherence tomography and full-field electroretinography (ERG). Detailed genetic testing was also performed. RESULTS: The child carried a homozygous mutation in POLG (c.911T > G/p.Leu304Arg) and manifested systemic features such as seizures, headaches, areflexia, hypotonia, myopathy and vomiting. The child's distance visual acuity was 0.50 and 0.40 LogMAR in the right and left eyes, respectively. Bilateral ophthalmoplegia and ptosis were observed at 5 years of age. The dark-adapted (DA) ERG responses to 2.29 cd s m-2 and 7.6 cd s m-2 stimuli showed a markedly reduced b/a ratio; an electronegative configuration was noted to a DA 7.6 ERG. CONCLUSION: This is the first documented case of an electronegative ERG in a POLG-related disorder consistent with generalized rod ON-bipolar dysfunction. The rest of the proband's systemic and ophthalmological features were consistent with SANDO but some features overlapped with other POLG-related disorders such as Alpers-Huttenlocher syndrome and autosomal dominant progressive external ophthalmoplegia demonstrating the wide phenotypic overlap expected due to POLG mutations.
OBJECTIVE: To report the clinical and novel electrophysiological features in a child with POLG-related sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO). METHODS: The proband, a male child of Indian descent, underwent serial systemic and ophthalmological evaluations from birth until 14 years of age. Eye examinations included visual acuity and extraocular movement assessments, fundus photography, spectral domain optical coherence tomography and full-field electroretinography (ERG). Detailed genetic testing was also performed. RESULTS: The child carried a homozygous mutation in POLG (c.911T > G/p.Leu304Arg) and manifested systemic features such as seizures, headaches, areflexia, hypotonia, myopathy and vomiting. The child's distance visual acuity was 0.50 and 0.40 LogMAR in the right and left eyes, respectively. Bilateral ophthalmoplegia and ptosis were observed at 5 years of age. The dark-adapted (DA) ERG responses to 2.29 cd s m-2 and 7.6 cd s m-2 stimuli showed a markedly reduced b/a ratio; an electronegative configuration was noted to a DA 7.6 ERG. CONCLUSION: This is the first documented case of an electronegative ERG in a POLG-related disorder consistent with generalized rod ON-bipolar dysfunction. The rest of the proband's systemic and ophthalmological features were consistent with SANDO but some features overlapped with other POLG-related disorders such as Alpers-Huttenlocher syndrome and autosomal dominant progressive external ophthalmoplegia demonstrating the wide phenotypic overlap expected due to POLG mutations.
Authors: Aleksandra Trifunovic; Anna Wredenberg; Maria Falkenberg; Johannes N Spelbrink; Anja T Rovio; Carl E Bruder; Mohammad Bohlooly-Y; Sebastian Gidlöf; Anders Oldfors; Rolf Wibom; Jan Törnell; Howard T Jacobs; Nils-Göran Larsson Journal: Nature Date: 2004-05-27 Impact factor: 49.962
Authors: Petri Luoma; Atle Melberg; Juha O Rinne; Jyrki A Kaukonen; Nina N Nupponen; Richard M Chalmers; Anders Oldfors; Ilkka Rautakorpi; Leena Peltonen; Kari Majamaa; Hannu Somer; Anu Suomalainen Journal: Lancet Date: 2004 Sep 4-10 Impact factor: 79.321
Authors: G C Kujoth; A Hiona; T D Pugh; S Someya; K Panzer; S E Wohlgemuth; T Hofer; A Y Seo; R Sullivan; W A Jobling; J D Morrow; H Van Remmen; J M Sedivy; T Yamasoba; M Tanokura; R Weindruch; C Leeuwenburgh; T A Prolla Journal: Science Date: 2005-07-15 Impact factor: 47.728
Authors: Weiming Zheng; Konstantin Khrapko; Hilary A Coller; William G Thilly; William C Copeland Journal: Mutat Res Date: 2006-02-20 Impact factor: 2.433
Authors: Yu X G Kong; Nicole Van Bergen; Ian A Trounce; Bang V Bui; Vicki Chrysostomou; Hayley Waugh; Algis Vingrys; Jonathan G Crowston Journal: Aging Cell Date: 2011-04-07 Impact factor: 9.304
Authors: G Van Goethem; P Luoma; M Rantamäki; A Al Memar; S Kaakkola; P Hackman; R Krahe; A Löfgren; J J Martin; P De Jonghe; A Suomalainen; B Udd; C Van Broeckhoven Journal: Neurology Date: 2004-10-12 Impact factor: 9.910