ABHD12

• Haploinsufficiency score: Gene associated with autosomal recessive phenotype
• Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
• Haploinsufficiency Phenotype: POLYNEUROPATHY, HEARING LOSS, ATAXIA, RETINITIS PIGMENTOSA, AND CATARACT; PHARC

Haploinsufficiency phenotype comments:

Biallelic loss of function mutations in ABHD12 are associated with autosomal recessive PHARC syndrome (polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and early-onset cataracts). Fiskerstrand et al., 2010 (PMID: 20797687) describe 19 affected individuals with homozygous mutations from 4 families. Chen et al., 2013 (PMID: 24027063) describe an individual who is a compound heterozygote for a frameshift and a 59 kilobase deletion of exon 1. Eisenberger et al., 2012 (PMID: 22938382) report a patient who was initially diagnosed with Usher syndrome, type 3 but was found to have ataxia on neurological exam after a homozygous nonsense mutation in ABHD12 was detected. Nishiguchi et al, 2014 (PMID: 24697911), in addition to patients with syndromic retinitis pigmentosa, report one family with ABHD12 mutations and non-syndromic retinitis pigmentosa, illustrating some phenotypic variability.

• Triplosensitivity score: 0
• Strength of Evidence (disclaimer): No evidence for dosage pathogenicity