title: Differentiating Alström from Bardet-Biedl syndrome (BBS) using systematic ciliopathy genes sequencing.
abstract: BACKGROUND
  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).
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors: Centre de Référence pour les Affections Rares en Génétique Ophtalmologique, CARGO, Hôpitaux Universitaires de Strasbourg, Strasbourg, France. k.aliferis@gmail.com
authors: K
authors: K
authors: Aliferis
authors: S
authors: S
authors: Hellé
authors: G
authors: G
authors: Gyapay
authors: S
authors: S
authors: Duchatelet
authors: C
authors: C
authors: Stoetzel
authors: J L
authors: JL
authors: Mandel
authors: H
authors: H
authors: Dollfus
mesh_terms: D056769:Alstrom Syndrome / Q000175:diagnosis* / Q000235:genetics*; D020788:Bardet-Biedl Syndrome / Q000175:diagnosis* / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D020417:Nystagmus, Congenital / Q000175:diagnosis / Q000235:genetics; D009765:Obesity / Q000175:diagnosis / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D011506:Proteins