Ciliopathy

A Ziliopathie is a genetic disease of the ciliated cells whose backbone (eg, the basal cells ) or a dysfunction of cilia.

Introduction

Since cilia occur on almost all cell types in vertebrates, the fundamental significance of this cell organelle is underlined. It facilitates the formation of a wide range of functionality. The main task lies in the sensory area, and a " driving force for fluid flows". In the sensory area the cilia play a role in the mechanoreception, the smell, the perception of light, in chemo - and thermo- receptors as well as in monitoring the osmotic pressure "motor for fluid flows" is intra-and extracellular influences for example, has the fluid transport in the kidney or the airways ( epithelium ). From this, the power of the participation of ciliopathies many illnesses guess. Dysfunction of cilia usually have an already noticeable in embryonic development. In the stem cell research to cells of mouse and man the formation of a primary cilium was observed. This primary cilium is at elementary signal transduction pathways such as Hedgehog ( Hh ) -, Wnt, PDGF and FGF signaling pathway involved. The absence of cilia on the differentiating cells seems to be more the exception. The presence of an intact and also differentiating Zilienapparates seems to be essential for cell line development, as primary processes of intercellular signaling pathways are dependent on it. Insights in this are so far in tests with mice and especially popular with aquarists zebrafish. Disturbances in the Hedgehog signaling pathway lead to defects of the neural tube, or a malformation of limb (Shh sub form). Impairments in the Wnt signaling pathway also lead to neural tube defects and changes in the stereocilia in the inner ear. For further Signalwegstörungen changes lead to the GPCR to form the Laurence -Moon -Biedl - Bardet syndrome. The formation of a polycystic kidney is related, inter alia, zilienabhängingen the PDGF receptor α. Disorders of mechanoreception was found in changes in the calcium - and cAMP - controlled responses, leading to left-right disturbances (eg, situs inversus ) and polycystic kidneys.

Ciliopathies are predominantly associated with proteins that previously were 2,500 identified that are associated with the cilia themselves or centrosomes. It is possible that other proteins, such as XPNPEP3, which is localized in mitochondria, presumably proteolytic changes in the Zilienproteinen, and thus disturbances that trigger.

Diseases

Further evidence of this disease group were obtained until the mid 1990 's, although many elements of cell organelles are still unclear in the various tissues. One research focus was and is the question of why disorders of cilia can cause serious illness such images. Since cilia are sitting at almost every cell and take over similar duties, the symptoms of disease overlap common and there are often found matching mutations at the same loci, the combination of mutations results in a different and / or additional Syndrome images

In healthy organisms are particularly " zilienkritische " areas:

• General development
• Homeostasis
• Fertility

Known ciliopathies

Other, secured ciliopathies

• Miscarriage (some cases )
• Hydrocephalus (some cases )
• Liver cyst
• Retinopathy ( some forms )

Suspected ciliopathies

Especially Badano formulated in his review article from 2006 for these diseases or partially for the symptoms rather globally held a Ziliopathie as a possible cause:

( Literature prior to 2008 until the end of 2011 no reliable confirmation of a PubMed search found)

• Corpus callosum agenesis
• Anencephaly
• Disorders of the respiratory
• Vermishypoplasie hypoplasia
• Dandy-Walker malformation
• Diabetes mellitus
• Ellis -van Creveld - Syndrome
• Exencephaly
• Eye movement disorders
• Liver disease
• Hypoplasia of the corpus callosum
• Hypotension
• Infertility
• Jeune syndrome ( asphyxische thoracic dystrophy )
• Juvenile myoclonic epilepsy ( JME )
• Mental retardation / developmental disability
• Obesity
• Polydactyly
• Posterior encephalocele
• Disorders of the respiratory system
• Recurrent respiratory infections
• Cystic kidney
• Retinitis pigmentosa ( some forms ) The publication of Khanna suggests that some forms of RP are now but should be seen rather as confirmed ciliopathies
• Hardness of hearing
• Situs inversus
• Spina bifida
• Marden -Walker syndrome
• Situs inversus