Ciliopathy
Encyclopedia
A ciliopathy is a genetic disorder
of the cellular
cilia
or the cilia anchoring structures, the basal bodies
, or of ciliary function.
Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosome
s, it is possible for ciliopathies to be associated with proteins such as XPNPEP3
, which localizes to mitochondria but is believed to affect ciliiary function through proteolytic cleavage of ciliary proteins.
Significant advances in understanding the importance of cilia were made beginning in the mid-1990s. However, "the physiological role that this organelle plays in most tissues remains elusive." Addition study of "how ciliary dysfunction can lead to such severe disease and developmental pathologies" is a subject of current research.
. Recent research has revealed an initial understanding that cilia are essential to many of the body's organs". Many mammal
ian eukaryotic
cells are ciliated
with primary cilia. These primary cilia play important roles in chemosensation
, mechanosensation
, and thermosensation. Cilia may thus be "viewed as sensory cellular antennae
that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation."
Recent advances in mammal
ian genetic research
have facilitated the elucidation of a molecular basis for a number of dysfunctional mechanisms in both motile and primary cilia structures of the cell
. "Numerous critical developmental signaling pathways" essential to cellular development have been discovered. These are principally but not exclusively found in the non-motile or primary cilia. A number of common observable characteristics
of mammalian genetic
disorders and diseases are caused by ciliary dysgenesis and dysfunction. Once identified, these characteristics thus describe a set of hallmarks of a ciliopathy.
Cilia have recently been implicated in a wide variety of human
genetic diseases by "the discovery that numerous protein
s involved in mammalian disease localize to the basal bodies and cilia." For example, in just a single area of human disease physiology, cystic renal disease, cilia-related genes and proteins have been identified to have causal effect in polycystic kidney disease
, nephronophthisis
, Senior-Loken syndrome type 5, orofaciodigital syndrome
type 1 and Bardet-Biedl syndrome
.
composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines." Cilia "function as mechano- or chemosensors and as a cellular global positioning system to detect changes in the surrounding environment." For example, ciliary signaling plays a role in the initiation of cellular replacement after cell damage.
In addition to this sensory role mediating specific signaling cues, cilia play "a secretory
role in which a soluble protein is released to have an effect downstream of the fluid flow" in epithelial cells, and can of course mediate fluid flow directly in the case of motile cilia. Primary cilia in the retina
play a role in transferring nourishment to the non-vascularized rod
and cone
cells from the vascularized
cells several micrometres behind the surface of the retina.
Signal transduction pathways involved include the Hedgehog signaling pathway
and the Wnt signaling pathway
.
are endeavoring to define functional modules containing multiple genes and then look at disorders whose phenotype
s fit into such modules.
A particular phenotype
can overlap "considerably with several conditions (ciliopathies) in which primary cilia are also implicated in pathogenicity
. One emerging
aspect is the wide spectrum of ciliopathy gene mutations found within different diseases."
that define a ciliopathy may be used to both recognize the cellular
basis of a number of genetic disorder
s and to facilitate the diagnosis and treatment of some diseases of unknown etiology
".
In organisms of normal health, cilia are critical for:
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
of the cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
cilia
Cilium
A cilium is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body....
or the cilia anchoring structures, the basal bodies
Basal body
A basal body is an organelle formed from a centriole, and a short cylindrical array of microtubules. It is found at the base of a eukaryotic undulipodium and serves as a nucleation site for the growth of the axoneme microtubules...
, or of ciliary function.
Although ciliopathies are usually considered to involve proteins that localize to the primary cilia or centrosome
Centrosome
In cell biology, the centrosome is an organelle that serves as the main microtubule organizing center of the animal cell as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden in 1883...
s, it is possible for ciliopathies to be associated with proteins such as XPNPEP3
XPNPEP3
Xaa-Pro aminopeptidase 3, also known as aminopeptidase P3, is an enzyme that in humans is encoded by the XPNPEP3 gene.- Function :...
, which localizes to mitochondria but is believed to affect ciliiary function through proteolytic cleavage of ciliary proteins.
Significant advances in understanding the importance of cilia were made beginning in the mid-1990s. However, "the physiological role that this organelle plays in most tissues remains elusive." Addition study of "how ciliary dysfunction can lead to such severe disease and developmental pathologies" is a subject of current research.
History
Although non-motile or primary cilia were first described in 1898, "cell biologists largely ignored them." But "microscopists continued to document their presence in the cells of most vertebrate organisms." The "primary cilium was long considered--with few exceptions--to be a largely useless evolutionary vestige, a vestigial organelleOrganelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....
. Recent research has revealed an initial understanding that cilia are essential to many of the body's organs". Many mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian eukaryotic
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
cells are ciliated
Cilium
A cilium is an organelle found in eukaryotic cells. Cilia are slender protuberances that project from the much larger cell body....
with primary cilia. These primary cilia play important roles in chemosensation
Chemosensor
A chemoreceptor, also known as chemosensor, is a sensory receptor that transduces a chemical signal into an action potential. In more general terms, a chemosensor detects certain chemical stimuli in the environment.- Classes :...
, mechanosensation
Mechanosensation
Mechanosensation is a response mechanism to mechanical stimuli. The physiological foundation for the senses of touch, hearing and balance, and pain is the conversion of mechanical stimuli into neuronal signals: mechanosensation. Mechanoreceptors of the skin, called cutaneous mechanoreceptors, are...
, and thermosensation. Cilia may thus be "viewed as sensory cellular antennae
Antenna (biology)
Antennae in biology have historically been paired appendages used for sensing in arthropods. More recently, the term has also been applied to cilium structures present in most cell types of eukaryotes....
that coordinate a large number of cellular signaling pathways, sometimes coupling the signaling to ciliary motility or alternatively to cell division and differentiation."
Recent advances in mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
ian genetic research
Research
Research can be defined as the scientific search for knowledge, or as any systematic investigation, to establish novel facts, solve new or existing problems, prove new ideas, or develop new theories, usually using a scientific method...
have facilitated the elucidation of a molecular basis for a number of dysfunctional mechanisms in both motile and primary cilia structures of the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. "Numerous critical developmental signaling pathways" essential to cellular development have been discovered. These are principally but not exclusively found in the non-motile or primary cilia. A number of common observable characteristics
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
of mammalian genetic
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
disorders and diseases are caused by ciliary dysgenesis and dysfunction. Once identified, these characteristics thus describe a set of hallmarks of a ciliopathy.
Cilia have recently been implicated in a wide variety of human
Human
Humans are the only living species in the Homo genus...
genetic diseases by "the discovery that numerous protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s involved in mammalian disease localize to the basal bodies and cilia." For example, in just a single area of human disease physiology, cystic renal disease, cilia-related genes and proteins have been identified to have causal effect in polycystic kidney disease
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
, nephronophthisis
Nephronophthisis
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease.The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure.It is a form of...
, Senior-Loken syndrome type 5, orofaciodigital syndrome
Orofaciodigital syndrome
Orofaciodigital syndrome 1 , also called Papillon-Leage and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.-Cause and...
type 1 and Bardet-Biedl syndrome
Bardet-Biedl syndrome
The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the...
.
The mechanism of ciliary function
"In effect, the [motile cilium] is a nanomachineMolecular machine
A molecular machine, or nanomachine, is any discrete number of molecular components that produce quasi-mechanical movements in response to specific stimuli . The expression is often more generally applied to molecules that simply mimic functions that occur at the macroscopic level...
composed of perhaps over 600 proteins in molecular complexes, many of which also function independently as nanomachines." Cilia "function as mechano- or chemosensors and as a cellular global positioning system to detect changes in the surrounding environment." For example, ciliary signaling plays a role in the initiation of cellular replacement after cell damage.
In addition to this sensory role mediating specific signaling cues, cilia play "a secretory
Secretion
Secretion is the process of elaborating, releasing, and oozing chemicals, or a secreted chemical substance from a cell or gland. In contrast to excretion, the substance may have a certain function, rather than being a waste product...
role in which a soluble protein is released to have an effect downstream of the fluid flow" in epithelial cells, and can of course mediate fluid flow directly in the case of motile cilia. Primary cilia in the retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...
play a role in transferring nourishment to the non-vascularized rod
Rod cell
Rod cells, or rods, are photoreceptor cells in the retina of the eye that can function in less intense light than can the other type of visual photoreceptor, cone cells. Named for their cylindrical shape, rods are concentrated at the outer edges of the retina and are used in peripheral vision. On...
and cone
Cone cell
Cone cells, or cones, are photoreceptor cells in the retina of the eye that are responsible for color vision; they function best in relatively bright light, as opposed to rod cells that work better in dim light. If the retina is exposed to an intense visual stimulus, a negative afterimage will be...
cells from the vascularized
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
cells several micrometres behind the surface of the retina.
Signal transduction pathways involved include the Hedgehog signaling pathway
Hedgehog signaling pathway
In a growing embryo, cells develop differently in the head or tail end of the embryo, the left or right, and other positions. They also form segments which develop into different body parts. The hedgehog signaling pathway gives cells information that they need to make the embryo develop properly....
and the Wnt signaling pathway
Wnt signaling pathway
The Wnt signaling pathway is a network of proteins best known for their roles in embryogenesis and cancer, but also involved in normal physiological processes in adult animals.-Discovery:...
.
Similar genes can result in a range of different diseases
"Just as different genes can contribute to similar diseases, so the same genes and families of genes can play a part in a range of different diseases." For example, in just two of the diseases caused by malfunctioning cilia, Meckel-Gruber syndrome and Bardet-Biedl syndrome, patients who carry mutations in genes associated with both diseases "have unique symptoms that are not seen in either condition alone." The genes linked to the two different conditions "interact with each other during development." Systems biologistsSystems biology
Systems biology is a term used to describe a number of trends in bioscience research, and a movement which draws on those trends. Proponents describe systems biology as a biology-based inter-disciplinary study field that focuses on complex interactions in biological systems, claiming that it uses...
are endeavoring to define functional modules containing multiple genes and then look at disorders whose phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s fit into such modules.
A particular phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
can overlap "considerably with several conditions (ciliopathies) in which primary cilia are also implicated in pathogenicity
Pathogenicity
Pathogenicity is the ability of a pathogen to produce an infectious disease in an organism.It is often used interchangeably with the term "virulence", although virulence is used more specifically to describe the relative degree of damage done by a pathogen, or the degree of pathogenicity caused by...
. One emerging
Emergence
In philosophy, systems theory, science, and art, emergence is the way complex systems and patterns arise out of a multiplicity of relatively simple interactions. Emergence is central to the theories of integrative levels and of complex systems....
aspect is the wide spectrum of ciliopathy gene mutations found within different diseases."
Ciliopathies
"The phenotypic parametersPhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
that define a ciliopathy may be used to both recognize the cellular
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
basis of a number of genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s and to facilitate the diagnosis and treatment of some diseases of unknown etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....
".
Other identified ciliopathies
- early embryonic deathEmbryoAn embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
(some cases) - hydrocephalusHydrocephalusHydrocephalus , also known as "water in the brain," is a medical condition in which there is an abnormal accumulation of cerebrospinal fluid in the ventricles, or cavities, of the brain. This may cause increased intracranial pressure inside the skull and progressive enlargement of the head,...
(some cases) - polycystic liver diseasePolycystic liver diseasePolycystic liver disease usually describes the presence of multiple cysts scattered throughout normal liver tissue, in association with polycystic kidney disease.-Pathophysiology:Associations with PRKCSH and SEC63 have been described....
- retinal degenerationRetinopathyRetinopathy is a general term that refers to some form of non-inflammatory damage to the retina of the eye. Frequently, retinopathy is an ocular manifestation of systemic disease.-Pathophysiology:Causes of retinopathy are varied:...
(some forms)
Implied or suspected ciliopathies
- agenesis of the corpus callosumAgenesis of the corpus callosumAgenesis of the corpus callosum is a rare birth defect in which there is a complete or partial absence of the corpus callosum. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally,...
- anencephalyAnencephalyAnencephaly is a cephalic disorder that results from a neural tube defect that occurs when the cephalic end of the neural tube fails to close, usually between the 23rd and 26th day of pregnancy, resulting in the absence of a major portion of the brain, skull, and scalp...
- breathingBreathingBreathing is the process that moves air in and out of the lungs. Aerobic organisms require oxygen to release energy via respiration, in the form of the metabolism of energy-rich molecules such as glucose. Breathing is only one process that delivers oxygen to where it is needed in the body and...
abnomalities - cerebellar vermisCerebellar vermisThe cerebellar vermis is located in the medial, cortico-nuclear zone of the cerebellum, residing in the posterior fossa of the cranium. The primary fissure in the vermis curves ventrolaterally to the superior surface of the cerebellum, dividing it into anterior and posterior lobes....
hypoplasiaHypoplasiaHypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia... - Dandy-Walker malformation
- diabetes
- Ellis-van Creveld syndromeEllis-van Creveld syndromeEllis–van Creveld Syndrome is a rare genetic disorder of the skeletal dysplasia type.-Symptoms:...
- exencephalyExencephalyExencephaly is a type of cephalic disorder wherein the brain is located outside of the skull. This condition is usually found in embryos as an early stage of anencephaly. As an exencephalic pregnancy progresses, the neural tissue gradually degenerates....
- eye movement abnormalities
- liver diseaseLiver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
- hypoplasiaHypoplasiaHypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
of the corpus callosumCorpus callosumThe corpus callosum , also known as the colossal commissure, is a wide, flat bundle of neural fibers beneath the cortex in the eutherian brain at the longitudinal fissure. It connects the left and right cerebral hemispheres and facilitates interhemispheric communication... - hypotoniaHypotoniaHypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
- reproductive sterilityInfertilityInfertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
- Jeune asphyxiating thoracic dystrophyDystrophyDystrophy is any condition of abnormal development, often denoting the degeneration of muscles.-Types:* Muscular dystrophy* Duchenne muscular dystrophy* Becker's muscular dystrophy* Reflex neurovascular dystrophy* Retinal dystrophy* Conal dystrophy...
- Juvenile myoclonic epilepsyJuvenile myoclonic epilepsyJuvenile myoclonic epilepsy , also known as Janz syndrome, is a fairly common form of idiopathic generalized epilepsy, representing 5-10% of all epilepsies. This disorder typically first manifests itself between the ages of 12 and 18 with myoclonus occurring early in the morning. Most patients also...
(JME) - Kartagener syndrome
- Marden-Walker syndromeMarden-Walker syndromeMarden–Walker syndrome is a rare autosomal recessive congenital disorder. It is characterized by blepharophimosis, microcephaly, micrognathia, multiple joint contractures, arachnodactyly, camptodactyly, kyphoscoliosis, and delayed motor development and is often associated with cystic dysplastic...
- "mental retardationMental retardationMental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
/developmental delay" or "other cognitive defectsCognitive deficitCognitive deficit, also known as cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to cognitive performance...
" - obesityObesityObesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
- polydactylyPolydactylyPolydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes....
- posterior encephaloceleEncephaloceleEncephalocele, sometimes known by the Latin name cranium bifidum, is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal...
- respiratory dysfunctionRespiratory systemThe respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
- "recurrent respiratory infections"
- renal cystic disease
- retinitis pigmentosaRetinitis pigmentosaRetinitis pigmentosa is a group of genetic eye conditions that leads to incurable blindness. In the progression of symptoms for RP, night blindness generally precedes tunnel vision by years or even decades. Many people with RP do not become legally blind until their 40s or 50s and retain some...
(some forms) - sensorineural deafness
- situs inversusSitus inversusSitus inversus is a congenital condition in which the major visceral organs are reversed or mirrored from their normal positions. The normal arrangement is known as situs solitus...
/Isomerism - spina bifidaSpina bifidaSpina bifida is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. Some vertebrae overlying the spinal cord are not fully formed and remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to protrude through...
Clinical symptoms and ciliary roles
A wide variety of symptoms are potential clinical features of ciliopathy.- Chemosensation abnormalities,, typically via ciliated epithelialEpitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cellular dysfunction. - Defective thermosensation or mechanosensationMechanosensationMechanosensation is a response mechanism to mechanical stimuli. The physiological foundation for the senses of touch, hearing and balance, and pain is the conversion of mechanical stimuli into neuronal signals: mechanosensation. Mechanoreceptors of the skin, called cutaneous mechanoreceptors, are...
, often via ciliated epithelialEpitheliumEpithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
cellular dysfunction. - Cellular motilityMotilityMotility is a biological term which refers to the ability to move spontaneously and actively, consuming energy in the process. Most animals are motile but the term applies to single-celled and simple multicellular organisms, as well as to some mechanisms of fluid flow in multicellular organs, in...
dysfunction - Issues with displacement of extracellular fluidExtracellular fluidExtracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...
- Paracrine signal transductionParacrine signallingParacrine signalling is a form of cell signalling in which the target cell is near the signal-releasing cell.-Local action:Some signalling molecules degrade very quickly, limiting the scope of their effectiveness to the immediate surroundings...
abnormalities
In organisms of normal health, cilia are critical for:
- organism developmentDevelopmental biologyDevelopmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis", which is the process that gives rise to tissues, organs and anatomy.- Related fields of study...
- homeostasisHomeostasisHomeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
- reproduction
External links
- The Ciliary Proteome Web Page at Johns Hopkins
- Katsanis Lab, The Center for Human Disease Modeling, Duke University
- Ciliopathy Alliance UK - alliance of medical researchers, doctors and patient organisations representing patients and families suffering from ciliopathy diseases
- Deafness Research UK - genetics and hearing loss links, including ciliopathy conditions