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Phenotype-Genotype Correlations in Bardet-Biedl Syndrome Patients with Molecular Analysis

  • Aslı Ece Solmaz
  • Hüseyin Onay
  • Tahir Atık
  • Ayça Aykut
  • Meltem Cerrah Güneş
  • Özge Özalp Yüreğir
  • Veysel Nijat Baş
  • Filiz Hazan
  • Özgür Kırbıyık
  • Ferda Özkinay

J Clin Res Pediatr Endocrinol 2015;7(2):82-82

Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive ciliopathy characterized by obesity, rod-cone dystrophy, postaxial polydactyly, renal and genital abnormalities, and learning difficulties. To date, mutations in 18 genes have been described to be responsible for BBS. In this study, we investigated 15 cases clinically diagnosed with BBS and the mutation distribution in 16 BBS genes using targeted next-generation sequencing and genotype-phenotype correlation. Mutation analysis of the 16 BBS genes (BBS1, BBS2, ARL6, BBS4, BBS5, MKKS, BBS7, TTC8, BBS9, BBS10, TRIM32, BBS12, MKS1, NPHP6, WDPCP, SDCCAG8) was performed with targeted next-generation sequencing in the 15 BBS cases. We discovered the disease-causing mutations in 13 of the 15 patients evaluated in this study. We identified the following mutations: in BBS1 gene - 1 previously reported (Y284SfsX5) and 2 novel (IVS1-3C>G, Q338X) mutations, in BBS2 gene - 1 novel mutation (G88AfsX6), in BBS4 gene - 1 novel mutation (IVS6-2A>G), in BBS7 gene - 1 previously reported (R238EfsX59) and 1 novel (L317V) mutations, in BBS9 gene - 1 novel mutation (N35X), in BBS10 gene - 1 previously reported (S311A) and 3 novel (K619IfsX10, I342NfsX20, T516NfsX8) mutations. The cases were evaluated with clinical findings and molecular genetic characteristics in terms of phenotype-genotype correlation. This is the first study investigating BBS molecular diagnosis and phenotype-genotype correlation in Turkey and one of the few studies in the world. Identification of molecular disorder in patients can help prevent the complications that may develop and contribute to growth of a healthy generation.

Keywords: Bardet-Biedl syndrome, next-generation sequencing, mutation, phenotype- genotype correlation