title: Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family.
abstract: OBJECTIVE
  Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP.
  
  
  METHODS
  We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes.
  
  
  RESULTS
  The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister.
  
  
  CONCLUSIONS
  We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression into severe visual impairment including central vision in the index and overall milder symptoms in the younger brother and sister.
authors: Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.
authors: Ditta
authors: D
authors: Zobor
authors: Department of Pathology and Histology, Al-Quds University, Eastern Jerusalem, Palestinian Authority.
authors: Ghassan
authors: G
authors: Balousha
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.
authors: Britta
authors: B
authors: Baumann
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Germany.
authors: Bernd
authors: B
authors: Wissinger
mesh_terms: D000328:Adult; D001482:Base Composition / Q000235:genetics; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D005654:Fundus Oculi; D005808:Genes, Recessive / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008877:Middle East; D008969:Molecular Sequence Data; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000235:genetics*; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C552553:FAM161A protein, human