OBJECTIVE: To identify the genetic causes underlying autosomal recessive 
retinitis pigmentosa (arRP) and to describe the associated phenotype.
DESIGN: Case series.
PARTICIPANTS: Three hundred forty-seven unrelated families affected by arRP and 
33 unrelated families affected by retinitis pigmentosa (RP) plus noncongenital 
and progressive hearing loss, ataxia, or both, respectively.
METHODS: A whole exome sequencing (WES) analysis was performed in 2 families 
segregating arRP. A mutational screening was performed in 378 additional 
unrelated families for the exon-intron boundaries of the ABHD12 gene. To 
establish a genotype-phenotype correlation, individuals who were homozygous or 
compound heterozygotes of mutations in ABHD12 underwent exhaustive clinical 
examinations by ophthalmologists, neurologists, and otologists.
MAIN OUTCOME MEASURES: DNA sequence variants, best-corrected visual acuity, 
visual field assessments, electroretinogram responses, magnetic resonance 
imaging, and audiography.
RESULTS: After a WES analysis, we identified 4 new mutations (p.Arg107Glufs*8, 
p.Trp159*, p.Arg186Pro, and p.Thr202Ile) in ABHD12 in 2 families (RP-1292 and 
W08-1833) previously diagnosed with nonsyndromic arRP, which cosegregated with 
the disease among the family members. Another homozygous mutation (p.His372Gln) 
was detected in 1 affected individual (RP-1487) from a cohort of 378 unrelated 
arRP and syndromic RP patients. After exhaustive clinical examinations by 
neurologists and otologists, the 4 affected members of the RP-1292 had no 
polyneuropathy or ataxia, and the sensorineural hearing loss and cataract were 
attributed to age or the normal course of the RP, whereas the affected members 
of the families W08-1833 and RP-1487 showed clearly symptoms associated with 
polyneuropathy, hearing loss, cerebellar ataxia, RP, and early-onset cataract 
(PHARC) syndrome.
CONCLUSIONS: Null mutations in the ABHD12 gene lead to PHARC syndrome, a 
neurodegenerative disease including polyneuropathy, hearing loss, cerebellar 
ataxia, RP, and early-onset cataract. Our study allowed us to report 5 new 
mutations in ABHD12. This is the first time missense mutations have been 
described for this gene. Furthermore, these findings are expanding the spectrum 
of phenotypes associated with ABHD12 mutations ranging from PHARC syndrome to a 
nonsyndromic form of retinal degeneration.