Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3
1 Bioscientia Center for Human Genetics, Konrad Adenauer-Str. 17, Ingelheim 55218, Germany
2 Department of Human Genetics, McGill University Health Center, Montreal, Canada
3 Department of Obstetrics and Gynecology, McGill University Health Center, Montreal, Canada
4 Department of Ophthalmology, American University of Beirut, Beirut, Lebanon
5 Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
6 Cologne Center for Genomics, University of Cologne, Cologne, Germany
7 Institute of Human Genetics, University Hospital of Cologne, Cologne, Germany
8 Department of Human Genetics, RWTH Aachen University, Aachen, Germany
9 Center for Clinical Research, University Hospital of Freiburg, Freiburg, Germany
Orphanet Journal of Rare Diseases 2012, 7:59 doi:10.1186/1750-1172-7-59Published: 2 September 2012
Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family.
Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing.
Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype.
Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (