title: Diverse clinical phenotypes associated with a nonsense mutation in FAM161A.
abstract: OBJECTIVE
  Mutations in the FAM161A gene have been reported in association with autosomal recessive retinitis pigmentosa (arRP) in several ethnic populations. This study aimed to assess the prevalence of FAM161A-related retinopathy in a British cohort and to characterise the phenotype associated with mutations in this gene.
  
  
  METHODS
  The FAM161A coding region and intron-exon boundaries were screened by Sanger sequencing in 120 retinitis pigmentosa (RP) patients (with likely autosomal recessive inheritance) in whom mutations in other known major RP genes have been ruled out by commercially available testing. Homozygosity mapping was performed in one consanguineous family, and high-throughput sequencing of candidate genes was performed to identify disease-associated changes. Clinical assessment of affected individuals included perimetry testing, fundus autofluorescence imaging, and optical coherence tomography.
  
  
  RESULTS
  Two patients of British origin with a homozygous mutation in FAM161A (c.1309A>T, p.Arg437*) were identified by Sanger sequencing. Homozygosity mapping and subsequent high-throughput sequencing analysis identified a further family of Pakistani origin with the same genotype. Clinical examination of affected members of these families revealed that this mutation was associated with a diverse clinical phenotype, ranging from mild disease with preservation of central acuity to severe visual impairment.
  
  
  CONCLUSIONS
  Homozygosity for the c.1309A>T, p.Arg437* variant in FAM161A is a relatively common cause of arRP. The mutation occurs in diverse ethnic populations, associated with typical retinitis pigmentosa with disease onset usually in the second or third decade of life.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Rose
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.|Department of Genetic Medicine, Central Manchester University Hospitals, Manchester, UK.
authors.forename: P
authors.initials: P
authors.lastname: Sergouniotis
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Alfano
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Muspratt-Tucker
authors.affiliation: Department of Genetic Medicine, Central Manchester University Hospitals, Manchester, UK.
authors.forename: S
authors.initials: S
authors.lastname: Barton
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.|Department of Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: A T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: Department of Genetic Medicine, Central Manchester University Hospitals, Manchester, UK.
authors.forename: G
authors.initials: G
authors.lastname: Black
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.|Department of Medical Retina Service, Moorfields Eye Hospital, London, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Webster
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D018389:Codon, Nonsense; D015331:Cohort Studies; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D015995:Prevalence; D012174:Retinitis Pigmentosa / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D006113:United Kingdom / Q000453:epidemiology; D014792:Visual Acuity / Q000502:physiology; D044465:White People / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; C552553:FAM161A protein, human