GGPS1-associated muscular dystrophy with and without hearing loss

Ann Clin Transl Neurol. 2022 Sep;9(9):1465-1474. doi: 10.1002/acn3.51633. Epub 2022 Jul 23.

Abstract

Ultra-rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra-rare missense variants in GGPS1 and provide follow-up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease-causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1-associated muscular dystrophy.

MeSH terms

  • Deafness*
  • Dimethylallyltranstransferase* / genetics
  • Farnesyltranstransferase / genetics
  • Female
  • Geranyltranstransferase / genetics
  • Hearing Loss* / genetics
  • Humans
  • Muscular Dystrophies* / genetics
  • Mutation, Missense
  • Primary Ovarian Insufficiency*

Substances

  • Dimethylallyltranstransferase
  • Geranyltranstransferase
  • Farnesyltranstransferase
  • GGPS1 protein, human