Intrafamilial “DOA-plus” phenotype variability related to different OMI/HTRA2 expression

Filomena Napolitano, Chiara Terracciano, Giorgia Bruno, Claudia Nesti, Maria R. Barillari, Umberto Barillari, Filippo M. Santorelli, Mariarosa A.B. Melone, Teresa Esposito, Simone Sampaolo

Research output: Contribution to journalArticlepeer-review

Abstract

Dominant Optic Atrophy and Deafness (DOAD) may be associated with one or more of the following disorders such as myopathy, progressive external ophthalmoplegia, peripheral neuropathy, and cerebellar atrophy (“DOA-plus”). Intra- and interfamilial variability of the “DOA-plus” phenotype is frequently observed in the majority of the patients carrying the same mutation in the OPA1 gene. We are describing two familial cases of “DOA-plus” carrying the same c.1334G>A (p.Arg445His) mutation in OPA1 and disclosing different clinical, pathological and biochemical features. The two patients showed different expression levels of the mitochondrial OMI/HTRA2 molecule, which acts as a mitochondrial stress sensor and has been described to interplay with OPA1 in in vitro studies. Our data offer the cue to inquire the role of OMI/HTRA2 as a modifier gene in determining the “DOAplus” phenotype variability.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
DOIs
Publication statusAccepted/In press - Jan 1 2019

Keywords

  • dominant optic atrophy and deafness (DOAD)
  • OMI/HTRA2 molecular studies
  • OPA1 gene and mutation analysis
  • phenotype intrafamilial variability
  • “DOAplus” phenotype

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Fingerprint

Dive into the research topics of 'Intrafamilial “DOA-plus” phenotype variability related to different OMI/HTRA2 expression'. Together they form a unique fingerprint.

Cite this