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Ciliopathies - from rare inherited cystic kidney diseases to basic cellular function.

Habbig S, Liebau MC - Mol Cell Pediatr (2015)

Bottom Line: Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment.While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research.According to the underlying cellular pathophysiology, these diverse disorders have been subsumed under the term "ciliopathies".

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Center for Molecular Medicine, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany. sandra.habbig@uk-koeln.de.

ABSTRACT

Background: Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment. While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research.

Findings: Cilia are nowadays considered to be crucial cellular structures controlling diverse intracellular signaling cascades. Dysfunction of cilia leads to a pleiotropic group of diseases ranging from cystic kidney disease via neurologic disorders to metabolic phenotypes and cardiac malformations. According to the underlying cellular pathophysiology, these diverse disorders have been subsumed under the term "ciliopathies".

Conclusions: The work on rare human ciliopathies has strongly deepened our genetic and cell biological understanding of multiple diseases and cellular events thus ultimately leading to clinical trials of novel therapeutic approaches. This review focuses on some of the important developments in ciliopathy research.

No MeSH data available.


Related in: MedlinePlus

Typical radiological findings in children with cystic kidney disease. (a, b) Typical ubiquitous macrocysts and enlarged kidney volumes are found a 15-year-old boy with ADPKD. (c) ARPKD typically presents with hyperechogenic kidney with microcysts as shown in a sonography of a 1-year-old boy. (d) The massively enlarged kidney volume in ARPKD is illustrated on axial abdominal MRI of a 10-month-old girl. (e) Ultrasonography of patients with nephronophthisis often shows small, hyperechogenic kidneys without corticomedullar differentiation. If present, cysts are typically found at the corticomedullar border. (f) Cerebellar vermis asplasia and elongated superior cerebellar peduncles result in the Molar Tooth Sign on axial MRI, which is pathognomonic for Joubert syndrome. ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease.
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Fig2: Typical radiological findings in children with cystic kidney disease. (a, b) Typical ubiquitous macrocysts and enlarged kidney volumes are found a 15-year-old boy with ADPKD. (c) ARPKD typically presents with hyperechogenic kidney with microcysts as shown in a sonography of a 1-year-old boy. (d) The massively enlarged kidney volume in ARPKD is illustrated on axial abdominal MRI of a 10-month-old girl. (e) Ultrasonography of patients with nephronophthisis often shows small, hyperechogenic kidneys without corticomedullar differentiation. If present, cysts are typically found at the corticomedullar border. (f) Cerebellar vermis asplasia and elongated superior cerebellar peduncles result in the Molar Tooth Sign on axial MRI, which is pathognomonic for Joubert syndrome. ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease.

Mentions: Understanding the pathophysiological events underlying rare genetic disorders has been a challenging task over a very long time, until the genetic revolution and novel techniques allowed high-throughput study approaches. As an example, the genetics of the mostly rare pediatric cystic kidney diseases remained very poorly understood. These disorders show a high degree of genotypic and phenotypic variability. Cystic kidney disease may present before birth like autosomal recessive polycystic kidney disease (ARPKD), during childhood and adolescence like nephronophthisis, or mostly in adults like the autosomal dominant polycystic kidney disease (ADPKD) which is one of the most frequent monogenetic diseases with an incidence of 1:1,000. Ciliopathies may show an isolated renal phenotype or may form part of a wide range of syndromes with partly overlapping renal and extrarenal clinical symptoms [1-4]. As an example, nephronophthisis may be found isolated, combined with retinitis pigmentosa in Senior-Løken syndrome or in a more severe syndrome with additional vermis asplasia in Joubert syndrome. Figure 1 aims to give an overview over the spectrum of diseases and clinical symptoms associated with genetic cystic kidney diseases. As pointed out in more detail below, multiple genes can be affected in disorders displaying cystic kidneys and the interplay of these genes strongly affects a patient’s phenotype. Examples of clinical symptoms are shown in Figure 2. For a more detailed description of clinical features, we refer to some of the excellent reviews on ciliopathies [1,5-7].Figure 1


Ciliopathies - from rare inherited cystic kidney diseases to basic cellular function.

Habbig S, Liebau MC - Mol Cell Pediatr (2015)

Typical radiological findings in children with cystic kidney disease. (a, b) Typical ubiquitous macrocysts and enlarged kidney volumes are found a 15-year-old boy with ADPKD. (c) ARPKD typically presents with hyperechogenic kidney with microcysts as shown in a sonography of a 1-year-old boy. (d) The massively enlarged kidney volume in ARPKD is illustrated on axial abdominal MRI of a 10-month-old girl. (e) Ultrasonography of patients with nephronophthisis often shows small, hyperechogenic kidneys without corticomedullar differentiation. If present, cysts are typically found at the corticomedullar border. (f) Cerebellar vermis asplasia and elongated superior cerebellar peduncles result in the Molar Tooth Sign on axial MRI, which is pathognomonic for Joubert syndrome. ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530564&req=5

Fig2: Typical radiological findings in children with cystic kidney disease. (a, b) Typical ubiquitous macrocysts and enlarged kidney volumes are found a 15-year-old boy with ADPKD. (c) ARPKD typically presents with hyperechogenic kidney with microcysts as shown in a sonography of a 1-year-old boy. (d) The massively enlarged kidney volume in ARPKD is illustrated on axial abdominal MRI of a 10-month-old girl. (e) Ultrasonography of patients with nephronophthisis often shows small, hyperechogenic kidneys without corticomedullar differentiation. If present, cysts are typically found at the corticomedullar border. (f) Cerebellar vermis asplasia and elongated superior cerebellar peduncles result in the Molar Tooth Sign on axial MRI, which is pathognomonic for Joubert syndrome. ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease.
Mentions: Understanding the pathophysiological events underlying rare genetic disorders has been a challenging task over a very long time, until the genetic revolution and novel techniques allowed high-throughput study approaches. As an example, the genetics of the mostly rare pediatric cystic kidney diseases remained very poorly understood. These disorders show a high degree of genotypic and phenotypic variability. Cystic kidney disease may present before birth like autosomal recessive polycystic kidney disease (ARPKD), during childhood and adolescence like nephronophthisis, or mostly in adults like the autosomal dominant polycystic kidney disease (ADPKD) which is one of the most frequent monogenetic diseases with an incidence of 1:1,000. Ciliopathies may show an isolated renal phenotype or may form part of a wide range of syndromes with partly overlapping renal and extrarenal clinical symptoms [1-4]. As an example, nephronophthisis may be found isolated, combined with retinitis pigmentosa in Senior-Løken syndrome or in a more severe syndrome with additional vermis asplasia in Joubert syndrome. Figure 1 aims to give an overview over the spectrum of diseases and clinical symptoms associated with genetic cystic kidney diseases. As pointed out in more detail below, multiple genes can be affected in disorders displaying cystic kidneys and the interplay of these genes strongly affects a patient’s phenotype. Examples of clinical symptoms are shown in Figure 2. For a more detailed description of clinical features, we refer to some of the excellent reviews on ciliopathies [1,5-7].Figure 1

Bottom Line: Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment.While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research.According to the underlying cellular pathophysiology, these diverse disorders have been subsumed under the term "ciliopathies".

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics and Center for Molecular Medicine, University Hospital of Cologne, Kerpener Straße 62, 50937, Cologne, Germany. sandra.habbig@uk-koeln.de.

ABSTRACT

Background: Primary cilia are membrane-bound microtubule-based protuberances of the cell membrane projecting to the extracellular environment. While little attention was paid to this subcellular structure over a long time, recent research has highlighted multiple cellular functions of primary cilia and has brought cilia to the focus of medical and cell biological research.

Findings: Cilia are nowadays considered to be crucial cellular structures controlling diverse intracellular signaling cascades. Dysfunction of cilia leads to a pleiotropic group of diseases ranging from cystic kidney disease via neurologic disorders to metabolic phenotypes and cardiac malformations. According to the underlying cellular pathophysiology, these diverse disorders have been subsumed under the term "ciliopathies".

Conclusions: The work on rare human ciliopathies has strongly deepened our genetic and cell biological understanding of multiple diseases and cellular events thus ultimately leading to clinical trials of novel therapeutic approaches. This review focuses on some of the important developments in ciliopathy research.

No MeSH data available.


Related in: MedlinePlus