Diverse clinical phenotypes associated with a nonsense mutation in FAM161A

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.

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.

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.

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.