title: LEBER CONGENITAL AMAUROSIS WITH LARGE RETINAL PIGMENT CLUMPS CAUSED BY COMPOUND HETEROZYGOUS MUTATIONS IN KCNJ13.
abstract: OBJECTIVE
  To describe a patient with mutations in KCNJ13 presenting particular clinical features.
  
  
  METHODS
  Standard ophthalmic examination, fundus autofluorescence, spectral domain optical coherence tomography, full-field electroretinography. The 3 exons of KCNJ13 were polymerase chain reaction amplified and Sanger sequenced.
  
  
  METHODS
  A 31-year-old man with Leber congenital amaurosis.
  
  
  RESULTS
  Patient had nystagmus since childhood, best-corrected visual acuity limited to 20/400 OD and 20/200 OS, and had cataracts extracted in both eyes. There were clumpy pigment deposits mostly in macular area, causing an uneven line of retinal pigment epithelium on spectral domain optical coherence tomography. In retinal parts devoid of pigment deposits around the optic disk and in periphery, retinal thickness was increased and hyperreflective formations were present either in the inner nuclear layer or in the outer nuclear layer. The patient was compound heterozygous for new mutations in KCNJ13 which encodes the Kir 7.1 potassium channel, c.314G>T (p.Ser105Ile) in exon 2 and c.655C>T (p.Gln219*) in exon 3. Both mutations were absent from databases.
  
  
  CONCLUSIONS
  KCNJ13 mutations are responsible for early-onset retinal dystrophy, featuring remarkable clumpy pigment deposits at the level of the retinal pigment epithelium, suggesting dysfunction and disorganization of this tissue. Parts of the retina remain relatively preserved anatomically but are increased in thickness. This distinct fundus appearance should help in identifying the "KCNJ13 retinal dystrophy" to orient the molecular diagnosis.
authors.affiliation: *Maladies Sensorielles Génétiques, CHRU, Montpellier, France; †INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France; ‡Université Montpellier, Montpellier, France; §Laboratory of Genetics in Ophthalmology, INSERM UMR 1163, Paris, France; and ¶Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Perez-Roustit
authors.forename: Virginie
authors.initials: V
authors.lastname: Marquette
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perrault
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005451:Fluorescein Angiography / Q000379:methods; D005654:Fundus Oculi; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics* / Q000378:metabolism; D012162:Retinal Degeneration / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology*; D041623:Tomography, Optical Coherence / Q000379:methods; D014792:Visual Acuity
chemical_list: C489477:Kir7.1 channel; D024661:Potassium Channels, Inwardly Rectifying