PUBLICATION

Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome

Authors
Leitch, C.C., Zaghloul, N.A., Davis, E.E., Stoetzel, C., Diaz-Font, A., Rix, S., Al-Fadhel, M., Lewis, R.A., Eyaid, W., Banin, E., Dollfus, H., Beales, P.L., Badano, J.L., and Katsanis, N.
ID
ZDB-PUB-080311-9
Date
2008
Source
Nature Genetics   40(4): 443-448 (Journal)
Registered Authors
Davis, Erica, Katsanis, Nicholas, Zaghloul, Norann A.
Keywords
none
MeSH Terms
  • Adult
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Antigens, Neoplasm/genetics*
  • Bardet-Biedl Syndrome/genetics*
  • Bardet-Biedl Syndrome/pathology
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism
  • Encephalocele/genetics*
  • Female
  • Gastrulation
  • Homozygote
  • Humans
  • Male
  • Membrane Proteins/genetics*
  • Molecular Sequence Data
  • Mutation/genetics*
  • Neoplasm Proteins/genetics*
  • Pedigree
  • Pregnancy
  • Proteins/genetics*
  • Sequence Homology, Amino Acid
  • Syndrome
  • Zebrafish/genetics
  • Zebrafish/growth & development*
  • Zebrafish/metabolism
PubMed
18327255 Full text @ Nat. Genet.
Abstract
Meckel-Gruber syndrome (MKS) is a genetically heterogeneous, neonatally lethal malformation and the most common form of syndromic neural tube defect (NTD). To date, several MKS-associated genes have been identified whose protein products affect ciliary function. Here we show that mutations in MKS1, MKS3 and CEP290 (also known as NPHP6) either can cause Bardet-Biedl syndrome (BBS) or may have a potential epistatic effect on mutations in known BBS-associated loci. Five of six families with both MKS1 and BBS mutations manifested seizures, a feature that is not a typical component of either syndrome. Functional studies in zebrafish showed that mks1 is necessary for gastrulation movements and that it interacts genetically with known bbs genes. Similarly, we found two families with missense or splice mutations in MKS3, in one of which the affected individual also bears a homozygous nonsense mutation in CEP290 that is likely to truncate the C terminus of the protein. These data extend the genetic stratification of ciliopathies and suggest that BBS and MKS, although distinct clinically, are allelic forms of the same molecular spectrum.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes