title: Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family.
abstract: To report the clinical and genetic findings of one family with autosomal recessive cone dystrophy (CD) and to identify the causative mutation.
  
  
  
  An institutional study of three family members from two generations. The clinical examination included best-corrected Snellen visual acuity measurement, fundoscopy, the Farnsworth D-15 color vision test, a full-field electroretinogram (ERG) that incorporated the International Society for Clinical Electrophysiology of Vision standards and methodology, fundus autofluorescence (FAF) and infrared (IR), and spectral-domain optical coherence tomography (SD-OCT). Genetic findings were achieved with DNA analysis using whole exome sequencing (WES) and Sanger sequencing.
  
  
  
  The proband, a 9-year-old boy, presented with a condition that appeared to be congenital and stationary. The clinical presentation initially reflected incomplete congenital stationary night blindness (icCSNB) because of myopia, a decrease in visual acuity, abnormal oscillatory potentials, and reduced amplitudes on the 30 Hz flicker ERG but was atypical because there were no clear electronegative responses. However, no disease-causing mutations in the genes underlying icCSNB were identified. Following WES analysis of family members, a homozygous splice-site mutation in intron 3 ofTTLL5(c.182-3_182-1delinsAA) was found cosegregating within the phenotype in the family.
  
  
  
  The distinction between icCSNB and CD phenotypes is not always straightforward in young patients. The patient was quite young, which most likely explains why the progression of the CD was not obvious. WES analysis provided prompt diagnosis for this family; thus, the use of this technique to refine the diagnosis is highlighted in this study.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 17 rue Moreau, Paris, France.
authors.forename: Miguel de Sousa
authors.initials: MS
authors.lastname: Dias
authors.affiliation: INSERM U 1051, Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, Montpellier, France; Affections Sensorielles Génétiques, CHU de Montpellier, 191 Avenue du Doyen Gaston Giraud, Montpellier, France; Université Montpellier, 163 Avenue Auguste Broussonnet, Montpellier, France.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
authors.affiliation: INSERM U 1051, Institut des Neurosciences de Montpellier, Hôpital Saint-Eloi, Montpellier, France; Affections Sensorielles Génétiques, CHU de Montpellier, 191 Avenue du Doyen Gaston Giraud, Montpellier, France; Université Montpellier, 163 Avenue Auguste Broussonnet, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 17 rue Moreau, Paris, France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Varin
authors.affiliation: IntegraGen SA, Genopole CAMPUS 1 bât, G8, EVRY, Paris, France.
authors.forename: Steven
authors.initials: S
authors.lastname: Blanchard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 17 rue Moreau, Paris, France.
authors.forename: Fiona
authors.initials: F
authors.lastname: Boyard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 17 rue Moreau, Paris, France; CHNO des Quinze-Vingts, DHU Sight Restore, INSERM-DHOS CIC1423, 28 rue de Charenton, Paris, France; Institute of Ophthalmology, University College of London, London EC1V 9EL, UK; Fondation Ophtalmologique Adolphe de Rothschild, Paris, France; Academie des Sciences, Institut de France, Paris, France; Department of Ophthalmology, The University of Pittsburghschool of Medicine, Pittsburg, PA.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM U968, CNRS UMR 7210, Institut de la Vision, 17 rue Moreau, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D020090:Chromosome Segregation / Q000235:genetics; D003241:Consanguinity; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D022821:RNA Splice Sites / Q000235:genetics*; D058499:Retinal Dystrophies / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D022821:RNA Splice Sites; C517816:TTLL5 protein, human