Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss

Sandra Iossa, Valerio Costa, Virginia Corvino, Gennaro Auletta, Luigi Barruffo, Stefania Cappellani, Carlo Ceglia, Giovanni Cennamo, Adamo Pio D'Adamo, Alessandra D'Amico, Nilde Di Paolo, Raimondo Forte, Paolo Gasparini, Carla Laria, Barbara Lombardo, Rita Malesci, Andrea Vitale, Elio Marciano, Annamaria Franzè

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Sensorineural hearing impairment is a common pathological manifestation in patients affected by X-linked intellectual disability. A few cases of interstitial deletions at Xq21 with several different phenotypic characteristics have been described, but to date, a complete molecular characterization of the deletions harboring disease-causing genes is still missing. Thus, the aim of this study is to realize a detailed clinical and molecular analysis of a family affected by syndromic X-linked hearing loss with intellectual disability. Results: Clinical analyses revealed a very complex phenotype that included inner ear malformations, vestibular problems, choroideremia and hypotonia with a peculiar pattern of phenotypic variability. Genomic analysis revealed, for the first time, the presence of two close interstitial deletions in the Xq21.1-21.3, harboring 11 protein coding, 9 non-coding genes and 19 pseudogenes. Among these, 3 protein coding genes have already been associated with X-linked hearing loss, intellectual disability and choroideremia. Conclusions: In this study we highlighted the presence of peculiar genotypic and phenotypic details in a family affected by syndromic X-linked hearing loss with intellectual disability. We identified two, previously unreported, Xq21.1-21.3 interstitial deletions. The two rearrangements, containing several genes, segregate with the clinical features, suggesting their role in the pathogenicity. However, not all the observed phenotypic features can be clearly associated with the known genes thus, further study is necessary to determine regions involved.

Original languageEnglish
Article number18
JournalMolecular Cytogenetics
Volume8
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • Choroideremia
  • Hypotonia
  • Intellectual disability
  • Interstitial deletions
  • X-linked hearing impairment

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Genetics(clinical)
  • Biochemistry
  • Molecular Medicine
  • Biochemistry, medical

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