Differentiating Alström from Bardet-Biedl syndrome (BBS) using systematic ciliopathy genes sequencing

Ophthalmic Genet. 2012 Mar;33(1):18-22. doi: 10.3109/13816810.2011.620055. Epub 2011 Oct 17.


Introduction: Early onset retinal degeneration associated with obesity can present a diagnostic challenge in paediatric ophthalmology practice. Clinical overlap between Bardet-Biedl syndrome (BBS) and Alström syndrome has been described, although the two entities are genetically distinct. To date, 16 genes are known to be associated with BBS (BBS1-16) and only one gene has been identified for Alström syndrome (ALMS1).

Materials and methods: In collaboration with the French National Center for Sequencing (CNS, Evry), all coding exons and flanking introns were sequenced for 27 ciliopathy genes (BBS1-12, MGC1203, TTC21b, AHI1, NPHP2-8 (NPHP6=BBS14), MKS1(BBS13), MKS3, C2ORF86, SDCCAG8, ALMS1) in 96 patients referred with a clinical diagnosis of BBS. ALMS1 gene analysis included sequencing of all coding exons.

Results: BBS known gene mutations were found in 44 patients (36 with two mutations and 8 heterozygous). ALMS1 mutations were found in four cases. The rate of ALMS1 mutations among patients suspected of having BBS was 4.2%.

Discussion: Clinically, all four patients presented early-onset severe retinal degeneration with congenital nystagmus associated with obesity. The difficult early differential diagnosis between the two syndromes is outlined. One mutation had already been reported (c.11310delAGAG/p.R3770fsX) and three were novel (c.2293C > T/p.Q765X, c.6823insA/p.R2275fsX, c.9046delA/p.N3016fsX).

Conclusions: Ciliopathy genes sequencing can be very helpful in providing a timely diagnosis in this group of patients, hence appropriate genetic counselling for families and adequate medical follow-up for affected children.

MeSH terms

  • Alstrom Syndrome / diagnosis*
  • Alstrom Syndrome / genetics*
  • Bardet-Biedl Syndrome / diagnosis*
  • Bardet-Biedl Syndrome / genetics*
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Exons / genetics
  • Female
  • Humans
  • Introns / genetics
  • Male
  • Mutation
  • Nystagmus, Congenital / diagnosis
  • Nystagmus, Congenital / genetics
  • Obesity / diagnosis
  • Obesity / genetics
  • Proteins / genetics*
  • Retinal Degeneration / diagnosis
  • Retinal Degeneration / genetics


  • ALMS1 protein, human
  • Cell Cycle Proteins
  • Proteins