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

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• 作者：Sandra Iossa (1) (2)
  Valerio Costa (3)
  Virginia Corvino (4)
  Gennaro Auletta (4)
  Luigi Barruffo (4)
  Stefania Cappellani (5)
  Carlo Ceglia (2)
  Giovanni Cennamo (6)
  Adamo Pio D鈥橝damo (5) (7)
  Alessandra D鈥橝mico (8)
  Nilde Di Paolo (8)
  Raimondo Forte (9)
  Paolo Gasparini (5) (7)
  Carla Laria (4)
  Barbara Lombardo (1) (2)
  Rita Malesci (4)
  Andrea Vitale (10)
  Elio Marciano (4)
  Annamaria Franz猫 (2) (4)
  
  1. DMMBM ; Universit脿 di Napoli 鈥淔ederico II鈥? Naples ; Italy
  2. Ceinge Biotecnologie Avanzate ; Naples ; Italy
  3. IGB 鈥淎. Buzzati Traverso鈥? CNR ; Naples ; Italy
  4. Istituto di Audiologia ; Dipartimento di Neuroscienze ; Scienze Riproduttive e Odontostomatologiche ; Universit脿 di Napoli 鈥淔ederico II鈥? Naples ; Italy
  5. Institute for Maternal and Child Health - IRCCS 鈥淏urlo Garofolo鈥? Trieste ; Italy
  6. Dipartimento di Oftalmologia ; Universit脿 di Napoli 鈥淔ederico II鈥? Naples ; Italy
  7. University of Trieste ; Trieste ; Italy
  8. Dipartimento di Scienze Biomediche Avanzate ; Universit脿 di Napoli 鈥淔ederico II鈥? Naples ; Italy
  9. Dipartimento di Oftalmologia Pediatrica ; Universit脿 di Salerno ; Salerno ; Italy
  10. Dipartimento di Scienze Motorie e del Benessere ; Universit脿 di Napoli 鈥淧arthenope鈥? Naples ; Italy
  
• 关键词：Choroideremia ; Hypotonia ; Interstitial deletions ; Intellectual disability ; X ; linked hearing impairment
• 刊名：Molecular Cytogenetics
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：8
• 期：1
• 全文大小：1,412 KB
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• 刊物主题：Cytogenetics; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1755-8166

文摘

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.