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Novel 25 kb Deletion of MERTK Causes Retinitis Pigmentosa With Severe Progression.
Evans, Daniel R; Green, Jane S; Johnson, Gordon J; Schwartzentruber, Jeremy; Majewski, Jacek; Beaulieu, Chandree L; Qin, Wen; Marshall, Christian R; Paton, Tara A; Roslin, Nicole M; Paterson, Andrew D; Fahiminiya, Somayyeh; French, Justin; Boycott, Kym M; Woods, Michael O.
Afiliación
  • Evans DR; Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • Green JS; Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • Johnson GJ; Department of Surgery (Ophthalmology), Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • Schwartzentruber J; Department of Human Genetics, McGill University, Montréal, Québec, Canada 4McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada.
  • Majewski J; Department of Human Genetics, McGill University, Montréal, Québec, Canada 4McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada.
  • Beaulieu CL; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • Qin W; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • Marshall CR; Program in Genetics and Genome Biology, The Center for Applied Genomics, The Hospital for Sick Children Research Institute, and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Paton TA; Program in Genetics and Genome Biology, The Center for Applied Genomics, The Hospital for Sick Children Research Institute, and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Roslin NM; Program in Genetics and Genome Biology, The Center for Applied Genomics, The Hospital for Sick Children Research Institute, and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Paterson AD; Program in Genetics and Genome Biology, The Center for Applied Genomics, The Hospital for Sick Children Research Institute, and Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
  • Fahiminiya S; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • French J; Western Memorial Regional Clinic (Eye Care Centre), Corner Brook, Newfoundland, Canada.
  • Boycott KM; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
  • Woods MO; Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
Invest Ophthalmol Vis Sci ; 58(3): 1736-1742, 2017 03 01.
Article en En | MEDLINE | ID: mdl-28324114
Purpose: Retinitis pigmentosa (RP) describes a complex group of inherited retinal dystrophies with almost 300 reported genes and loci. We investigated the genetic etiology of autosomal recessive RP (arRP) in a large kindred with 5 affected family members, who reside on the island of Newfoundland, Canada. Methods: Genetic linkage analysis was performed on 12 family members (Infinium HumanOmni2.5-8 BeadChip). Whole exome sequencing analysis (Illumina HiSeq) was performed on one affected individual. A custom pipeline was applied to call, annotate, and filter variants. FishingCNV was used to scan the exome for rare copy number variants (CNVs). Candidate CNVs subsequently were visualized from microarray data (CNVPartition v.3.1.6.). MERTK breakpoints were mapped and familial cosegregation was tested using Sanger Sequencing. Results: We found strong evidence of linkage to a locus on chromosome 2 (logarithm of the odds [LOD] 4.89 [θ = 0]), at an interval encompassing the MERTK gene. Whole exome sequencing did not uncover candidate point mutations in MERTK, or other known RP genes. Subsequently, CNV analysis of the exome data and breakpoint mapping revealed a 25,218 bp deletion of MERTK, encompassing exons 6 to 8, with breakpoints in introns 5 (chr2:112,725,292) and 8 (chr2:112,750,421). A 48 bp insertion sequence was buried within the breakpoint; 18 bps shared homology to MIR4435-2HG and LINC00152, and 30 bp mapped to MERTK. The deletion cosegregated with arRP in the family. Conclusions: This study describes the molecular and clinical characterization of an arRP family segregating a novel 25 kb deletion of MERTK. These findings may assist clinicians in providing a diagnosis for other unsolved RP cases.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Retinitis Pigmentosa / Proteínas Proto-Oncogénicas / Eliminación de Secuencia / Proteínas Tirosina Quinasas Receptoras Tipo de estudio: Diagnostic_studies / Etiology_studies Límite: Female / Humans / Male Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Retinitis Pigmentosa / Proteínas Proto-Oncogénicas / Eliminación de Secuencia / Proteínas Tirosina Quinasas Receptoras Tipo de estudio: Diagnostic_studies / Etiology_studies Límite: Female / Humans / Male Idioma: En Revista: Invest Ophthalmol Vis Sci Año: 2017 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos