title: Novel compound heterozygous TULP1 mutations in a family with severe early-onset retinitis pigmentosa.
abstract: OBJECTIVE
  To describe the clinical characteristics and determine the genetic defect in a Surinamese family with autosomal recessive retinitis pigmentosa.
  
  
  METHODS
  Family members underwent blood sampling and ophthalmologic examinations. After exclusion of all known mutations in all genes involved in autosomal recessive retinitis pigmentosa, a genome-wide linkage scan was performed using 11,555 single-nucleotide polymorphisms spread throughout the genome. Mutation analysis of the TULP1 gene was performed by direct sequencing.
  
  
  RESULTS
  All affected family members had a severe retinal dystrophy with a history of nystagmus, low visual acuity, and nyctalopia since infancy. The scotopic and photopic responses were nonrecordable on electroretinography. A genome-wide scan suggested linkage to the chromosomal region containing the TULP1 gene. Mutation analysis of TULP1 identified novel compound heterozygous mutations (p.Arg482Trp and p.Leu504fsX140) in all affected family members.
  
  
  CONCLUSIONS
  The affected members of the Surinamese family have a severe early-onset form of autosomal recessive retinitis pigmentosa, which is caused by compound heterozygous mutations in the TULP1 gene. Clinical Relevance Clinical and molecular genetic characterization of autosomal recessive retinitis pigmentosa may help to provide a more accurate prognosis in individual patients. This study confirms that TULP1 mutations cause a severe early-onset form of autosomal recessive retinitis pigmentosa.
authors.affiliation: Department of Human Genetics, Radboud University, Nijmegen Medical Centre, Nijmegen, the Netherlands. a.denhollander@antrg.umcn.nl
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Janneke J C
authors.initials: JJ
authors.lastname: van Lith-Verhoeven
authors.forename: Maarten L
authors.initials: ML
authors.lastname: Arends
authors.forename: Tim M
authors.initials: TM
authors.lastname: Strom
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009755:Night Blindness / Q000235:genetics; D009759:Nystagmus, Pathologic / Q000235:genetics; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012174:Retinitis Pigmentosa / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C105443:TULP1 protein, human