A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review

Gene. 2019 Jul 1:704:113-120. doi: 10.1016/j.gene.2019.04.008. Epub 2019 Apr 8.

Abstract

Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12.

Keywords: ABHD12; Novel nonsense variant; PHARC syndrome; Usher syndrome.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Ataxia / genetics
  • Ataxia / pathology
  • Cataract / genetics
  • Cataract / pathology
  • Child
  • Codon, Nonsense*
  • Exome Sequencing
  • Family
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Homozygote
  • Humans
  • Male
  • Monoacylglycerol Lipases / genetics*
  • Pedigree
  • Phenotype
  • Polyneuropathies / genetics
  • Polyneuropathies / pathology
  • Retinitis Pigmentosa / genetics
  • Retinitis Pigmentosa / pathology
  • Usher Syndromes / genetics*
  • Usher Syndromes / pathology

Substances

  • Codon, Nonsense
  • ABHD12 protein, human
  • Monoacylglycerol Lipases

Supplementary concepts

  • Polyneuropathy, Hearing Loss, Ataxia, Retinitis Pigmentosa, And Cataract