, 10:49 | Cite as

Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles

  • Stefania Zampieri
  • Mirella Filocamo
  • Emanuele Buratti
  • Marina Stroppiano
  • Kristian Vlahovicek
  • Natalia Rosso
  • Eleonora Bignulin
  • Stefano Regis
  • Franco Carnevale
  • Bruno Bembi
  • Andrea Dardis
Original Article


We report the molecular characterization of 12 unrelated Italian patients affected with Sandhoff disease (SD), a recessively inherited disorder caused by mutations in HEXB gene. We identified 11 different mutations of which six are novel: one large deletion of 2,406 nt, (c.299+1471_408del2406), one frameshift mutation c.965delT (p.I322fsX32), one nonsense c.1372C>T (p.Q458X), and three splicing mutations (c.299G>T, c.300-2A>G and c.512-1G>T). One allele was only characterized at the messenger RNA (mRNA) level (r = 1170_1242del). Real-time polymerase chain reaction analysis of the HEXB mRNA from fibroblasts derived from patients carrying the novel point mutations showed that the presence of the premature termination codon in the transcript bearing the mutation c.965delT triggers the nonsense-mediated decay (NMD) pathway, which results in the degradation of the aberrant mRNA. The presence of the c.299G>T mutation leads to the degradation of the mutated mRNA by a mechanism other than NMD, while mutations c.300-2A>G and c.512-1G>T cause the expression of aberrant transcripts. In our group, the most frequent mutation was c.850C>T (p.R284X) representing 29% of the alleles. Haplotype analysis suggested that this mutation did not originate from a single genetic event. Interestingly, the common 16-kb deletion mutation was absent. This work provides valuable information regarding the molecular genetics of SD in Italy and provides new insights into the molecular basis of the disease.


GM2 gangliosidosis Sandhoff disease HEXB gene Mutation analysis 


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Stefania Zampieri
    • 1
  • Mirella Filocamo
    • 2
  • Emanuele Buratti
    • 3
  • Marina Stroppiano
    • 2
  • Kristian Vlahovicek
    • 4
  • Natalia Rosso
    • 5
  • Eleonora Bignulin
    • 1
  • Stefano Regis
    • 2
  • Franco Carnevale
    • 6
  • Bruno Bembi
    • 1
    • 7
  • Andrea Dardis
    • 1
  1. 1.Unità di Malattie MetabolicheIRCCS Burlo GarofoloTriesteItaly
  2. 2.Laboratorio Diagnosi Pre-Postnatale Malattie MetabolicheIRCCS G. GasliniGenovaItaly
  3. 3.International Centre for Genetic Engineering and BiotechnologyTriesteItaly
  4. 4.Bioinformatics Unit, Molecular Biology Department, Division of BiologyFaculty of ScienceZagrebCroatia
  5. 5.Centro Studi FegatoTriesteItaly
  6. 6.UO Malattie Metaboliche-Genetica ClinicaOspedale Pediatrico “Giovanni XXIII”BariItaly
  7. 7.Regional Coordinator Centre for Rare DiseasesUniversity Hospital “Santa Maria della Misericordia”UdineItaly

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