The authors declare no conflict of interest.
Combining fetal sonography with genetic and allele pathogenicity studies to secure a neonatal diagnosis of Bardet–Biedl syndrome
Article first published online: 14 OCT 2012
© 2012 John Wiley & Sons A/S
Volume 83, Issue 6, pages 553–559, June 2013
How to Cite
Combining fetal sonography with genetic and allele pathogenicity studies to secure a neonatal diagnosis of Bardet–Biedl syndrome., , , , .
- Issue published online: 23 APR 2013
- Article first published online: 14 OCT 2012
- Accepted manuscript online: 21 SEP 2012 12:55PM EST
- Manuscript Accepted: 17 SEP 2012
- Manuscript Revised: 16 SEP 2012
- Manuscript Received: 30 JUL 2012
- National Institutes of Health (NIH). Grant Number: R01-EY021872
- National Eye Institute. Grant Number: R01HD04260
- National Institute of Child Health and Development. Grant Number: R01DK072301, R01DK075972
- National Institute of Diabetes Digestive and Kidney Disorders
- European Union (EU-SYSCILIA)
- Bardet–Biedl syndrome;
- variant functional analysis
Bardet–Biedl syndrome (BBS) is a rare pediatric ciliopathy characterized by marked clinical variability and extensive genetic heterogeneity. Typical diagnosis of BBS is secured at a median of 9 years of age, and sometimes well into adolescence. Here, we report a patient in whom prenatal detection of increased nuchal fold, enlarged echogenic kidneys, and polydactyly prompted us to screen the most commonly mutated genes in BBS and the phenotypically and genetically overlapping ciliopathy, Meckel–Gruber syndrome (MKS). We identified the common Met390Arg mutation in BBS1 in compound heterozygosity with a novel intronic variant of unknown significance (VUS). Testing of mRNA harvested from primary foreskin fibroblasts obtained shortly after birth revealed the VUS to induce a cryptic splice site, which in turn led to a premature termination and mRNA degradation. To our knowledge, this is the earliest diagnosis of BBS in the absence of other affected individuals in the family, and exemplifies how combining clinical assessment with genetic and timely assays of variant pathogenicity can inform clinical diagnosis and assist with patient management in the prenatal and neonatal setting.