Meckel's syndrome - Gruber ( English Meckel – Gruber syndrome ) - the genetic pathology of the person belonging to the group of ciliopathies . First described by a German physician Johann Meckel in 1822.
| Meckel-Gruber syndrome | |
|---|---|
| ICD-9-KM | and |
| Omim | 249000 |
| Diseasesdb | |
Clinical Symptoms
Meckel-Gruber syndrome belongs to the Finnish population, that is, it is almost exclusively observed in Finland . The incidence rate in Finnish newborns is 1: 9000. For the clinical diagnosis of the syndrome, four primary symptoms are necessary - polycystic kidney disease , anomalies in the development of the central nervous system (occipital encephalocele ), fibrotic changes in the liver and polydactyly .
Molecular genetic mechanisms
Mekel-Gruber syndrome is a genetically heterogeneous, autosomal recessive disease. To date, 10 genes are known whose mutations can lead to the development of the syndrome.
| Phenotype | Gene | Chromosomal locus |
|---|---|---|
| Meckel Syndrome - Gruber 1 | MKS1 | 17q22 |
| Meckel Syndrome - Grubera 2 | TMEM216 | 11q13 |
| Meckel Syndrome - Grubera 3 | TMEM67 | 8q |
| Meckel Syndrome - Grubera 4 | Cep290 | 12q |
| Meckel Syndrome - Grubera 5 | RPGRIP1L | 16q12.2 |
| Meckel Syndrome - Grubera 6 | CC2D2A | 4p15 |
| Meckel Syndrome - Grubera 7 | NPHP3 | 3q22 |
| Meckel Syndrome - Grubera 8 | TCTN2 | 12q24.31 |
| Meckel Syndrome - Grubera 9 | B9D1 | 17p11.2 |
| Meckel Syndrome - Grubera 10 | B9D2 | 19q13 |
According to recent studies, MKS proteins are necessary for the functioning of the so-called. "Transition zone", a Y-shaped structure at the base of cilia (basal body), connecting the axonema microtubules with the surrounding cell membrane . Proteins of the MKS module form a transit zone in parallel with the IFT- dependent axoneme formation, i.e. preventing non-cilic proteins from entering cilia. In other words, MKS proteins play the role of an intra-filial filter.
MKS proteins are necessary for the functioning of the so-called. "Transition zone" of cilia (TZ), acting as an intra-cilia filter
Localization of MKS1 protein in centrioles / basal body of cilia. Image obtained by immunofluorescence analysis
- ↑ 1 2 Disease Ontology release 2019-08-22 - 2019-08-22 - 2019.