E Héon

University of Toronto, Toronto, Ontario, Canada

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Publications (74)402.73 Total impact

  • Annals of surgery 06/2015; DOI:10.1097/SLA.0000000000001284 · 8.33 Impact Factor
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    ABSTRACT: Retinal gene therapy for Leber’s congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss of photoreceptors in the treated retina was the same as that in the untreated retina. Here we describe long-term follow-up data from three treated patients. Topographic maps of visual sensitivity in treated regions, nearly 6 years after therapy for two of the patients and 4.5 years after therapy for the third patient, indicate progressive diminution of the areas of improved vision.
    New England Journal of Medicine 05/2015; DOI:10.1056/NEJMoa1412965 · 55.87 Impact Factor
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    Elizabeth N. Kerr · Aparna Bhan · Elise Héon
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    ABSTRACT: Objective To investigate the behavioral phenotype of patients affected with Bardet-Biedl syndrome (BBS).Study designTwenty-four patients with molecularly confirmed diagnosis of BBS (6–38 years of age) were evaluated using standardized neuropsychological tests. Results were compared to normative data.ResultsThe mean intellectual functioning of participants fell 1½ standard deviations below normal expectations; though, the majority of participants (75-80%) did not display an Intellectual Disability. The group's mean performance on most cognitive tasks and all scales of adaptive functioning was significantly weaker than norms. The majority (55-60%) of participants displayed broadly-average verbal fluency and auditory rote learning, while 22-40% were severely impaired in the same areas. The majority of participants were severely impaired in perceptual reasoning (53%), attentional capacity (69%), and functional independence (74%). Symptoms associated with Autism were reported for 77% of participants. Behavioral issues were unrelated to intellectual ability but significantly correlated with adaptive functioning.Conclusion This first neurocognitive evaluation of a molecularly confirmed cohort of BBS patients shows that the majority of patients experience significant difficulties with perceptual intellectual abilities, auditory attentional capacity, adaptive independence, and behavior. The frequency of Autism-related symptoms far exceeds the incidence rate of diagnosed Autism in general and warrants further investigations.
    Clinical Genetics 05/2015; DOI:10.1111/cge.12614 · 3.93 Impact Factor
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    ABSTRACT: Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.
    Investigative Ophthalmology &amp Visual Science 02/2015; 56(2):918-31. DOI:10.1167/iovs.14-16049 · 3.40 Impact Factor
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    ABSTRACT: PRPS1 codes for the enzyme phosphoribosyl pyrophosphate synthetase-1 (PRS-1). The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2). We describe a novel phenotype associated with decreased PRS-1 function in two affected male siblings. Using whole exome and Sanger sequencing techniques, we identified a novel missense mutation in PRPS1. The clinical phenotype in our patients is characterized by high prenatal maternal α-fetoprotein, intrauterine growth restriction, dysmorphic facial features, severe intellectual disability and spastic quadraparesis. Additional phenotypic features include macular coloboma-like lesions with retinal dystrophy, severe short stature and diabetes insipidus. Exome sequencing of the two affected male siblings identified a shared putative pathogenic mutation c.586C>T p.(Arg196Trp) in the PRPS1 gene that was maternally inherited. Follow-up testing showed normal levels of hypoxanthine in urine samples and uric acid levels in blood serum. The PRS activity was significantly reduced in erythrocytes of the two patients. Nucleotide analysis in erythrocytes revealed abnormally low guanosine triphosphate and guanosine diphosphate. This presentation is the most severe form of PRPS1-deficiency syndrome described to date and expands the spectrum of PRPS1-related disorders.European Journal of Human Genetics advance online publication, 25 June 2014; doi:10.1038/ejhg.2014.112.
    European journal of human genetics: EJHG 06/2014; 23(3). DOI:10.1038/ejhg.2014.112 · 4.35 Impact Factor
  • Annals of Surgery 05/2014; 261(1). DOI:10.1097/SLA.0000000000000748 · 8.33 Impact Factor
  • Cancer Research 08/2013; 73(8 Supplement):958-958. DOI:10.1158/1538-7445.AM2013-958 · 9.33 Impact Factor
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    ABSTRACT: Purpose: Mutations in ZEB1 have been reported in posterior polymorphous corneal dystrophy (PPCD3; MIM #609141) and Fuchs' endothelial corneal dystrophy (FECD6; MIM #613270). Although PPCD and keratoconus are clinically and pathologically distinct, PPCD has been associated with keratoconus, suggesting a common genetic basis. The purpose of our study was to perform mutational screening of the ZEB1 gene in patients affected with keratoconus or PPCD. Methods: Sanger sequencing of ZEB1 was performed in 70 unrelated patients with keratoconus and 18 unrelated patients with PPCD. Real-time quantitative PCR (RT-qPCR) was performed on RNA from cultured corneal keratocytes obtained from a keratoconic patient harboring a missense ZEB1 mutation (p.Gln640His) undergoing corneal transplantation. Results: Mutational analysis of ZEB1 in PPCD identified a previously reported frameshift mutation (C.1578_1579INSG) and a novel nonsense mutation (C.2249C A) in exon 7 of ZEB1 causing the insertion of a stop codon: p.Ser750X. In the keratoconus cohort, a novel heterozygous pathogenic mutation in exon 7 (c.1920G > T; p.Gln640His) of ZEB1 was identified in a family affected with keratoconus and Fuchs' endothelial corneal dystrophy. RT-qPCR performed on cultured corneal keratocytes harboring the missense ZEB1 mutation (p.Gln640His) demonstrated that COL4A1 and COL4A2 were markedly downregulated, and COL4A3, COL4A4, and COL8A2 were moderately downregulated. Conclusions: Our data combined with the previously reported mutational spectrum of ZEB1 support a genotypephenotype correlation: missense substitutions in the ZEB1 protein are associated with FECD6 and keratoconus, whereas protein truncating ZEB1 mutations result in PPCD3. The dysregulation of α-type IV collagens represents a common link between ZEB1 mutation and the clinical phenotypes (PPCD3, FECD, and keratoconus).
    Investigative ophthalmology & visual science 04/2013; 54(5). DOI:10.1167/iovs.13-11781 · 3.40 Impact Factor
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    ABSTRACT: Purpose: To report phenotypic characteristics including macular cone photoreceptor morphology in KCNV2-related "cone dystrophy with supernormal rod electroretinogram" (CDSR). Methods: Seven patients, aged 9 to 18 years at last visit, with characteristic full-field electroretinographic (ERG) features of CDSR were screened for mutations in the KCNV2 gene. All patients underwent detailed ophthalmological evaluation, which included distance and color vision testing, contrast sensitivity measurement, fundus photography, fundus autofluorescence (FAF) imaging, and spectral domain-optical coherence tomography (SD-OCT). Follow-up visits were available in six cases. Rod photoreceptor function was assessed using a bright white flash ERG protocol (240 cd·s/m(2)). Macular cone photoreceptor morphology was assessed from 2° by 2° zonal images obtained using adaptive optics scanning laser ophthalmoscopy (AOSLO) in six cases. Results: Pathogenic mutations in KCNV2 were identified in all seven cases. Best corrected vision was 20/125 or worse in all cases at the latest visit (20/125-20/400). Vision loss was progressive in two cases. Color vision and contrast sensitivity was abnormal in all cases. Retinal exam revealed minimal pigment epithelial changes at the fovea in four cases. A peri- or parafoveal ring of hyperfluorescence was the most common FAF abnormality noted (five cases). The SD-OCT showed outer retinal abnormalities in all cases. The rod photoreceptor maximal response was reduced but rod sensitivity was normal. AOSLO showed markedly reduced cone density in all six patients tested. Conclusions: Central vision parameters progressively worsen in CDSR. Structural retinal and lipofuscin accumulation abnormalities are commonly present. Macular cone photoreceptor mosaic is markedly disrupted early in the disease.
    Investigative ophthalmology & visual science 12/2012; 54(1). DOI:10.1167/iovs.12-10971 · 3.40 Impact Factor
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    ABSTRACT: Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.Trp169*) and missense (c.769G>A, p.Glu257Lys) mutations in NMNAT1, which encodes an enzyme in the nicotinamide adenine dinucleotide (NAD) biosynthesis pathway implicated in protection against axonal degeneration. We also found NMNAT1 mutations in ten other individuals with LCA, all of whom carry the p.Glu257Lys variant.
    Nature Genetics 07/2012; 44(9):972-4. DOI:10.1038/ng.2370 · 29.35 Impact Factor
  • A Vincent · E Héon
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    ABSTRACT: Eye is the official journal of the Royal College of Ophthalmologists. It aims to provide the practising ophthalmologist with information on the latest clinical and laboratory-based research.
    Eye (London, England) 06/2012; 26(9):1278-80. DOI:10.1038/eye.2012.125 · 2.08 Impact Factor
  • Cancer Research 06/2012; 72(8 Supplement):809-809. DOI:10.1158/1538-7445.AM2012-809 · 9.33 Impact Factor
  • Cancer Research 07/2011; 71(8 Supplement):694-694. DOI:10.1158/1538-7445.AM2011-694 · 9.33 Impact Factor
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    ABSTRACT: To determine the role of ultrasound biomicroscopy (UBM) in the management of children affected with retinoblastoma. A review of clinical records of children with the diagnosis of retinoblastoma at the Hospital for Sick Children from January 1995 to December 2007, for whom UBM was used to determine the extent of intraocular tumor. Clinical characteristics were compared with UBM. Pathological correlation was performed for enucleated eyes. In total, 101 eyes of 75 patients were included in the final analysis. Only 11 eyes were diagnosed on UBM to have extension of the tumor anterior to the ora serrata, and were enucleated. Histopathological examination confirmed the anterior extension in all the 11 eyes. In total, 50 eyes were enucleated because of various reasons, such as poor visual prognosis (12 eyes), unilateral group D or E (23 eyes), recurrences (8 eyes), and treatment failure (7 eyes). None of those patients were found to have anterior extension of the disease on histopathological examination. UBM did not yield any false negative (0/50) or any false positives (0/11). The UBM provided a sensitive and reproducible visualization of the anterior retina, ciliary region, and anterior segment allowing a better staging of the advanced disease process. Primary assessment of the true extent of retinoblastoma is critical for the selection of an optimal management approach.
    Eye (London, England) 02/2011; 25(2):141-7. DOI:10.1038/eye.2010.193 · 2.08 Impact Factor
  • Cancer Research 01/2011; 70(8 Supplement):3535-3535. DOI:10.1158/1538-7445.AM10-3535 · 9.33 Impact Factor
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    ABSTRACT: To describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation. A retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1 gene. A heterozygous change, p.V86M (c.256G > A), was identified in the BEST1 gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from ≥ 20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n = 2), microcornea with shallow anterior chamber (n = 1), iris dysgenesis (n = 2), cataracts (n = 4), classical peripheral concentric band of retinal hyperpigmentation (n = 5), and optic nerve dysplasia (n = 1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years). ADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC.
    Eye (London, England) 11/2010; 25(1):113-8. DOI:10.1038/eye.2010.165 · 2.08 Impact Factor
  • CA Mok · E Héon · M Zhen
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    ABSTRACT: Obesity associates with increased health risks such as heart disease, stroke and diabetes. The steady rise in the obese population worldwide poses an increasing burden on health systems. Genetic factors contribute to the development of obesity, and the elucidation of their physiological functions helps to understand the cause, and improve the prevention, diagnosis and treatment for this disorder. Primary cilia are evolutionarily conserved organelles whose dysfunctions lead to human disorders now defined as ciliopathies. Human ciliopathies present pleiotropic and overlapping phenotypes that often include retinal degeneration, cystic renal anomalies and obesity. Increasing evidence implicates an intriguing involvement of cilia in lipid/energy homeostasis. Here we discuss recent studies in support of the key roles of ciliary genes in the development and pathology of obesity in various animal models. Genes affecting ciliary development and function may pose promising candidate underlying genetic factors that contribute to the development of common obesity.
    Clinical Genetics 11/2009; 77(1):18-27. DOI:10.1111/j.1399-0004.2009.01305.x · 3.93 Impact Factor
  • Elise Héon
    Canadian Journal of Ophthalmology 10/2009; 44(5):506-7. DOI:10.3129/i09-177 · 1.33 Impact Factor
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    ABSTRACT: To perform mutational screening of the visual system homeobox gene 1 (VSX1; MIM#605020) in patients with sporadic and familial keratoconus (MIM#148300) in a European population and, for the first time, report the mutational analysis of the two newly identified VSX1exons. VSX1sequence variants in patients with keratoconus were evaluated by direct sequencing of the entire coding region, including two novel exons. In familial keratoconus cases, segregation of potentially pathogenic VSX1variants was assessed to determine pathogenicity. Transcript analysis was carried out on splice site and synonymous sequence variants not detected in controls. A total of 66 unrelated patients with keratoconus from the European population (27 with familial keratoconus; 39 with sporadic keratoconus) were analysed for VSX1 mutations. Four sequence variants were not observed in 100 healthy control individuals: c.432C>G (p.D144E), c.479G>A (p.G160D), c.789C>T (p.S263S), and an intronic change c.844-13T>A (numbered with respect to NM_014588). Segregation was not detected for p.D144E and c.844-13T>A. The change in p.G160D was observed in two patients with sporadic keratoconus. Although predicted to alter VSX1 splicing, p.S263S had no effect on transcript processing. Four known SNPs were detected and the following polymorphic variants were observed in keratoconus patients and controls: c.711T>A (NM_199425; p.P237P), c.844-5_-6insT (NM_014588), c.*28G>T (DQ854811/DQ854812), and c.*50G>A (DQ854809/DQ854810). VSX1has a minor role in keratoconus pathogenesis. The pathogenicity of p.G160D remains controversial and this change may represent a rare polymorphism or genetic modifier. Further evidence is provided that the previously reported variant, p.D144E, is a polymorphism.
    Eye (London, England) 09/2009; 24(6):1085-92. DOI:10.1038/eye.2009.217 · 2.08 Impact Factor

Publication Stats

2k Citations
402.73 Total Impact Points


  • 1996–2015
    • University of Toronto
      • • Department of Ophthalmology and Vision Sciences
      • • Hospital for Sick Children
      Toronto, Ontario, Canada
  • 2001–2013
    • SickKids
      • Department of Ophthalmology and Vision Sciences
      Toronto, Ontario, Canada
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 2003
    • University Health Network
      Toronto, Ontario, Canada
  • 1997
    • University Hospital of Lausanne
      Lausanne, Vaud, Switzerland