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


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
Publication statusAccepted/In press - Jan 1 2019


  • 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)


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