title: Cone dystrophy in patient with homozygous RP1L1 mutation.
abstract: The purpose of this study was to determine whether an autosomal recessive cone dystrophy was caused by a homozygous RP1L1 mutation. A family including one subject affected with cone dystrophy and four unaffected members without evidence of consanguinity underwent detailed ophthalmic evaluations. The ellipsoid and interdigitation zones on the spectral-domain optical coherence tomography images were disorganized in the proband. The proband had a reduced amplitude of cone and flicker full-field electroretinograms (ERGs). Focal macular ERGs and multifocal ERGs were severely reduced in the proband. A homozygous RP1L1 mutation (c.3628T>C, p.S1210P) was identified in the proband. Family members who were heterozygous for the p.S1210P mutation had normal visual acuity and normal results of clinical evaluations. To investigate other putative pathogenic variant(s), a next-generation sequencing (NGS) approach was applied to the proband. NGS identified missense changes in the heterozygous state of the PCDH15, RPGRIP1, and GPR98 genes. None of these variants cosegregated with the phenotype and were predicted to be benign reinforcing the putative pathogenicity of the RP1L1 homozygous mutation. The AO images showed a severe reduction of the cone density in the proband. Our findings indicate that a homozygous p.S1210P exchange in the RP1L1 gene can cause cone dystrophy.
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Inzai, Chiba 270-1694, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kikuchi
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Inzai, Chiba 270-1694, Japan.
authors.forename: Shuhei
authors.identifier: 0000-0003-3962-3099
authors.initials: S
authors.lastname: Kameya
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Inzai, Chiba 270-1694, Japan.
authors.forename: Kiyoko
authors.identifier: 0000-0002-9661-8993
authors.initials: K
authors.lastname: Gocho
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC Université Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Said
authors.initials: S
authors.lastname: El Shamieh
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Inzai, Chiba 270-1694, Japan.
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Akeo
authors.affiliation: Honjo Daiichi Hospital, Yurihonjo, Akita 015-0834, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sugawara
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Chiba Hokuso Hospital, Inzai, Chiba 270-1694, Japan.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yamaki
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC Université Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France.
authors.forename: Christina
authors.identifier: 0000-0002-3510-1712
authors.initials: C
authors.lastname: Zeitz
authors.affiliation: INSERM, U968, 75012 Paris, France ; Sorbonne Universités, UPMC Université Paris 06, UMR_S 968, Institut de la Vision, 75012 Paris, France ; CNRS, UMR_7210, 75012 Paris, France ; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, 75012 Paris, France.
authors.forename: Isabelle
authors.identifier: 0000-0003-0698-5309
authors.initials: I
authors.lastname: Audo
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D019943:Amino Acid Substitution; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D005136:Eye Proteins; C474032:RP1L1 protein, human