title: Phenotypic and genetic characterization of a family carrying two Xq21.1-21.3 interstitial deletions associated with syndromic hearing loss.
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.
authors.affiliation: DMMBM, Università di Napoli "Federico II", Naples, Italy ; Ceinge Biotecnologie Avanzate, Naples, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Iossa
authors.affiliation: IGB "A. Buzzati Traverso", CNR, Naples, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Costa
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Corvino
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Auletta
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Barruffo
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Cappellani
authors.affiliation: Ceinge Biotecnologie Avanzate, Naples, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Ceglia
authors.affiliation: Dipartimento di Oftalmologia, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cennamo
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy ; University of Trieste, Trieste, Italy.
authors.forename: Adamo Pio
authors.initials: AP
authors.lastname: D'Adamo
authors.affiliation: Dipartimento di Scienze Biomediche Avanzate, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Dipartimento di Scienze Biomediche Avanzate, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Nilde
authors.initials: N
authors.lastname: Di Paolo
authors.affiliation: Dipartimento di Oftalmologia Pediatrica, Università di Salerno, Salerno, Italy.
authors.forename: Raimondo
authors.initials: R
authors.lastname: Forte
authors.affiliation: Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy ; University of Trieste, Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Laria
authors.affiliation: DMMBM, Università di Napoli "Federico II", Naples, Italy ; Ceinge Biotecnologie Avanzate, Naples, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Lombardo
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Malesci
authors.affiliation: Dipartimento di Scienze Motorie e del Benessere, Università di Napoli "Parthenope", Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vitale
authors.affiliation: Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Marciano
authors.affiliation: Ceinge Biotecnologie Avanzate, Naples, Italy ; Istituto di Audiologia, Dipartimento di Neuroscienze, Scienze Riproduttive e Odontostomatologiche, Università di Napoli "Federico II", Naples, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Franzè
keywords: Choroideremia; Hypotonia; Intellectual disability; Interstitial deletions; X-linked hearing impairment
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