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

@article{Leitch2008HypomorphicMI,
  title={Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome},
  author={Carmen C. Leitch and Norann A Zaghloul and Erica E. Davis and Corinne Stoetzel and Anna D{\'i}az-Font and Suzanne Rix and Majid Alfadhel and Richard Alan Lewis and Wafaa Eyaid and Eyal Banin and H{\'e}l{\`e}ne Dollfus and Philip Beales and Jos{\'e} L. Badano and Nicholas Katsanis},
  journal={Nature Genetics},
  year={2008},
  volume={40},
  pages={443-448}
}
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… Expand
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TLDR
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TLDR
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TLDR
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TLDR
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References

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Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome.
Meckel syndrome (MKS) is a rare autosomal recessive lethal condition characterized by central nervous system malformations, polydactyly, multicystic kidney dysplasia, and ductal changes of the liver.Expand
The Meckel-Gruber syndrome gene, MKS3, is mutated in Joubert syndrome.
TLDR
It is hypothesized that mutations in the recently identified MKS genes, MKS1 on chromosome 17q and MKS3 on 8q, may be a cause of Joubert syndrome, and mutation analysis ofMKS1 andMKS3 was identified in a series of patients with JS, thus defining MKSS3 as the sixth JS locus (JBTS6). Expand
The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat
TLDR
Meckel-Gruber syndrome is a severe autosomal, recessively inherited disorder characterized by bilateral renal cystic dysplasia, developmental defects of the central nervous system, hepatic ductal Dysplasia and cysts and polydactyly, and a previously uncharacterized, evolutionarily conserved gene that is expressed at moderate levels in fetal brain, liver and kidney but has widespread, low levels of expression. Expand
Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype‐phenotype correlation
TLDR
It is indicated that the MKS1 and MKS3 genes are each responsible for about 7% of MKS cases with various mutations in different populations, and a strong phenotype‐genotype correlation was observed regarding the type of central nervous system malformation, the frequency of polydactyly, bone dysplasia, and situs inversus. Expand
The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome
TLDR
Findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder. Expand
Mutations in MKKS cause obesity, retinal dystrophy and renal malformations associated with Bardet-Biedl syndrome
TLDR
The data suggest that a complete loss of function of the MKKS product, and thus an inability to fold a range of target proteins, is responsible for the clinical manifestations of BBS. Expand
Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior–Løken syndrome
TLDR
Six novel and six known truncating mutations, one known missense mutation and one novel 3 bp pair in-frame deletion were identified in a total of seven families with JBTS, two families with SLSN and one family with isolated NPHP. Expand
Triallelic Inheritance in Bardet-Biedl Syndrome, a Mendelian Recessive Disorder
TLDR
It is proposed that BBS may be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype, and this triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders. Expand
The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.
TLDR
Co-immunoprecipitation experiments show that wild-type meckelin and MKS1 interact and, in three-dimensional tissue culture assays, epithelial branching morphogenesis was severely impaired, suggesting that MKS proteins mediate a fundamental developmental stage of ciliary formation and epithelial morphogenesis. Expand
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis.
TLDR
The CEP290 mutations represent one of the most frequent causes of LCA identified so far and are localized in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). Expand
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