Meckel Syndrome, Type 1 Proteine (MKS1)

Human Meckel Syndrome, Type 1 (MKS1) Interaktionspartner

1. we have described a pathogenic variant in the MKS1 resulting in a mild Joubert syndrome phenotype, which broadens the spectrum of mutations in the MKS1.

2. Dnah11(avc)(4) did not disrupt SHF Hh signaling and caused Atrioventricular septal defects (AVSDs) only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1(avc)(6) disrupted SHF Hh signaling and caused AVSDs without heterotaxy.We speculate that cilia gene mutations contribute to both syndromic and non-syndromic AVSDs in humans

3. MKS1 functions in the transition zone at the base of the cilium to regulate ciliary INPP5E content.

4. describe four patients with mild Joubert phenotypes who carry pathogenic mutations in either MKS1 or B9D1, two genes previously implicated only in Meckel syndrome

5. identification of a gene, MKS1,(Meckel syndrome) mutated in MKS families linked to 17q.

6. The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.

7. Study concluded that MKS1 and MKS3 account for the majority of Meckel-Gruber syndrome; polydactyly is usually found in MKS1 but rare in MKS3; cases with no, or milder, CNS phenotypes were only found in MKS3.

8. genotyping of MKS1 & MKS3 genes in a large, multiethnic cohort of 120 independent cases of Meckel syndrome; first results indicate that the MKS1 & MKS3 genes are each responsible for about 7% of MKS cases with various mutations in different populations

9. Our results indicate that MKS1 mutations are not restricted to the Caucasian gene pool and suggest splicing defects are a crucial mutational mechanism in MKS1, and further genetic heterogeneity for MKS.

10. Mutations in MKS1 is associated with Bardet-Biedl syndrome

11. MKS-1 and MKS-1-related proteins 1 and 2 (MKSR-1, MKSR-2), localize to transition zones/basal bodies of sensory cilia; subcellular localization is largely co-dependent, pointing to a functional relationship between the proteins

12. Kidney tissue and cells from MKS1 and MKS3 patients showed defects in centrosome and cilia number, including multi-ciliated respiratory-like epithelia, and longer cilia.

Mouse (Murine) Meckel Syndrome, Type 1 (MKS1) Interaktionspartner

1. demonstrated that the MKS transition zone complex cooperates with the BBSome to mediate trafficking of specific trans-membrane receptors to the cilium

2. Dnah11(avc)(4) did not disrupt SHF Hh signaling and caused Atrioventricular septal defects (AVSDs) only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1(avc)(6) disrupted SHF Hh signaling and caused AVSDs without heterotaxy.We speculate that cilia gene mutations contribute to both syndromic and non-syndromic AVSDs in humans

3. Centriole localization of Mks1 is required for ciliogenesis of motile and non-motile cilia, but not for centriole assembly.

4. Mks1 is required for ciliogenesis and shh signaling in mouse model of human meckel syndrome.

5. Mks1 expression in mouse embryos, as determined by in situ hybridization, agrees well with the tissue phenotype of MKS.