bowang0911/MedQuAD huggingface dataset:
Gnathodiaphyseal dysplasia is caused by mutations in the ANO5 gene, which provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Studies suggest that most anoctamin channels are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear.  The ANO5 gene mutations that have been identified in people with gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these protein changes lead to the fragile bones, jaw problems, and other skeletal abnormalities that occur in gnathodiaphyseal dysplasia. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.
Primary spontaneous pneumothorax is an abnormal accumulation of air in the space between the lungs and the chest cavity (called the pleural space) that can result in the partial or complete collapse of a lung. This type of pneumothorax is described as primary because it occurs in the absence of lung disease such as emphysema. Spontaneous means the pneumothorax was not caused by an injury such as a rib fracture. Primary spontaneous pneumothorax is likely due to the formation of small sacs of air (blebs) in lung tissue that rupture, causing air to leak into the pleural space. Air in the pleural space creates pressure on the lung and can lead to its collapse. A person with this condition may feel chest pain on the side of the collapsed lung and shortness of breath.  Blebs may be present on an individual's lung (or lungs) for a long time before they rupture. Many things can cause a bleb to rupture, such as changes in air pressure or a very sudden deep breath. Often, people who experience a primary spontaneous pneumothorax have no prior sign of illness; the blebs themselves typically do not cause any symptoms and are visible only on medical imaging. Affected individuals may have one bleb to more than thirty blebs. Once a bleb ruptures and causes a pneumothorax, there is an estimated 13 to 60 percent chance that the condition will recur.
Mutations in the FLCN gene can cause primary spontaneous pneumothorax, although these mutations appear to be a very rare cause of this condition. The FLCN gene provides instructions for making a protein called folliculin. In the lungs, folliculin is found in the connective tissue cells that allow the lungs to contract and expand when breathing. Folliculin is also produced in cells that line the small air sacs (alveoli). Researchers have not determined the protein's function, but they believe it may help control the growth and division of cells. Folliculin may play a role in repairing and re-forming lung tissue following damage. Researchers have not determined how FLCN gene mutations lead to the formation of blebs and increase the risk of primary spontaneous pneumothorax. One theory is that the altered folliculin protein may trigger inflammation within the lung tissue that could alter and damage the tissue, causing blebs.  Primary spontaneous pneumothorax most often occurs in people without an identified gene mutation. The cause of the condition in these individuals is often unknown. Tall young men are at increased risk of developing primary spontaneous pneumothorax; researchers suggest that rapid growth of the chest during growth spurts may increase the likelihood of forming blebs. Smoking can also contribute to the development of primary spontaneous pneumothorax.
When this condition is caused by mutations in the FLCN gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases, a person inherits the FLCN gene mutation from an affected parent. People who have an FLCN gene mutation associated with primary spontaneous pneumothorax all appear to develop blebs, but it is estimated that only 40 percent of those individuals go on to have a primary spontaneous pneumothorax.
These resources address the diagnosis or management of primary spontaneous pneumothorax:  - Genetic Testing Registry: Pneumothorax, primary spontaneous  - MedlinePlus Encyclopedia: Chest Tube Insertion  - MedlinePlus Encyclopedia: Collapsed Lung  - Merck Manual for Patients and Caregivers   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Hereditary paraganglioma-pheochromocytoma is a condition characterized by the growth of noncancerous (benign) tumors in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. A tumor involving the paraganglia is known as a paraganglioma. A type of paraganglioma known as a pheochromocytoma develops in the adrenal glands, which are located on top of each kidney and produce hormones in response to stress. Other types of paraganglioma are usually found in the head, neck, or trunk. People with hereditary paraganglioma-pheochromocytoma develop one or more paragangliomas, which may include pheochromocytomas.  Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Sympathetic paragangliomas found outside the adrenal glands, usually in the abdomen, are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating.  Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing.  Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.  Researchers have identified four types of hereditary paraganglioma-pheochromocytoma, named types 1 through 4. Each type is distinguished by its genetic cause. People with types 1, 2, and 3 typically develop paragangliomas in the head or neck region. People with type 4 usually develop extra-adrenal paragangliomas in the abdomen and are at higher risk for malignant tumors that metastasize. Hereditary paraganglioma-pheochromocytoma is typically diagnosed in a person's 30s.
Mutations in at least four genes increase the risk of developing the different types of hereditary paraganglioma-pheochromocytoma. Mutations in the SDHD gene predispose an individual to hereditary paraganglioma-pheochromocytoma type 1; mutations in the SDHAF2 gene predispose to type 2; mutations in the SDHC gene predispose to type 3; and mutations in the SDHB gene predispose to type 4.  The SDHB, SDHC, and SDHD genes provide instructions for making three of the four subunits of an enzyme called succinate dehydrogenase (SDH). In addition, the protein made by the SDHAF2 gene is required for the SDH enzyme to function. The SDH enzyme links two important cellular pathways called the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. These pathways are critical in converting the energy from food into a form that cells can use.  As part of the citric acid cycle, the SDH enzyme converts a compound called succinate to another compound called fumarate. Succinate acts as an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia).  Mutations in the SDHB, SDHC, SDHD, and SDHAF2 genes lead to the loss or reduction of SDH enzyme activity. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. As a result, the hypoxia pathways are triggered in normal oxygen conditions, which lead to abnormal cell growth and tumor formation.
Hereditary paraganglioma-pheochromocytoma is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors. An additional mutation that deletes the normal copy of the gene is needed to cause the condition. This second mutation, called a somatic mutation, is acquired during a person's lifetime and is present only in tumor cells.  The risk of developing hereditary paraganglioma-pheochromocytoma types 1 and 2 is passed on only if the mutated copy of the gene is inherited from the father. The mechanism of this pattern of inheritance is unknown. The risk of developing types 3 and 4 can be inherited from the mother or the father.
These resources address the diagnosis or management of hereditary paraganglioma-pheochromocytoma:  - Gene Review: Gene Review: Hereditary Paraganglioma-Pheochromocytoma Syndromes  - Genetic Testing Registry: Paragangliomas 1  - Genetic Testing Registry: Paragangliomas 2  - Genetic Testing Registry: Paragangliomas 3  - Genetic Testing Registry: Paragangliomas 4  - MedlinePlus Encyclopedia: Pheochromocytoma  - National Cancer Institute: Pheochromocytoma and Paraganglioma   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Arterial tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the body, including blood vessels, skin, joints, and the gastrointestinal tract.  As its name suggests, arterial tortuosity syndrome is characterized by blood vessel abnormalities, particularly abnormal twists and turns (tortuosity) of the blood vessels that carry blood from the heart to the rest of the body (the arteries). Tortuosity arises from abnormal elongation of the arteries; since the end points of the arteries are fixed, the extra length twists and curves. Other blood vessel abnormalities that may occur in this disorder include constriction (stenosis) and abnormal bulging (aneurysm) of vessels, as well as small clusters of enlarged blood vessels just under the skin (telangiectasia).  Complications resulting from the abnormal arteries can be life-threatening. Rupture of an aneurysm or sudden tearing (dissection) of the layers in an arterial wall can result in massive loss of blood from the circulatory system. Blockage of blood flow to vital organs such as the heart, lungs, or brain can lead to heart attacks, respiratory problems, and strokes. Stenosis of the arteries forces the heart to work harder to pump blood and may lead to heart failure. As a result of these complications, arterial tortuosity syndrome is often fatal in childhood, although some individuals with mild cases of the disorder live into adulthood.  Features of arterial tortuosity syndrome outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features include joints that are either loose and very flexible (hypermobile) or that have deformities limiting movement (contractures), and unusually soft and stretchable skin. Some affected individuals have long, slender fingers and toes (arachnodactyly); curvature of the spine (scoliosis); or a chest that is either sunken (pectus excavatum) or protruding (pectus carinatum). They may have protrusion of organs through gaps in muscles (hernias), elongation of the intestines, or pouches called diverticula in the intestinal walls.  People with arterial tortuosity syndrome often look older than their age and have distinctive facial features including a long, narrow face with droopy cheeks; eye openings that are narrowed (blepharophimosis) with outside corners that point downward (downslanting palpebral fissures); a beaked nose with soft cartilage; a high, arched roof of the mouth (palate); a small lower jaw (micrognathia); and large ears. The cornea, which is the clear front covering of the eye, may be cone-shaped and abnormally thin (keratoconus).
Arterial tortuosity syndrome is caused by mutations in the SLC2A10 gene. This gene provides instructions for making a protein called GLUT10. The level of GLUT10 appears to be involved in the regulation of a process called the transforming growth factor-beta (TGF-) signaling pathway. This pathway is involved in cell growth and division (proliferation) and the process by which cells mature to carry out special functions (differentiation). The TGF- signaling pathway is also involved in bone and blood vessel development and the formation of the extracellular matrix, an intricate lattice of proteins and other molecules that forms in the spaces between cells and defines the structure and properties of connective tissues.  SLC2A10 gene mutations that cause arterial tortuosity syndrome reduce or eliminate GLUT10 function. By mechanisms that are not well understood, a lack (deficiency) of functional GLUT10 protein leads to overactivity (upregulation) of TGF- signaling. Excessive growth signaling results in elongation of the arteries, leading to tortuosity. Overactive TGF- signaling also interferes with normal formation of the connective tissues in other parts of the body, leading to the additional signs and symptoms of arterial tortuosity syndrome.
These resources address the diagnosis or management of arterial tortuosity syndrome:  - Gene Review: Gene Review: Arterial Tortuosity Syndrome  - Genetic Testing Registry: Arterial tortuosity syndrome  - Johns Hopkins McKusick-Nathans Institute of Genetic Medicine  - National Heart, Lung, and Blood Institute: How is an Aneurysm Treated?   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Deafness and myopia syndrome is a disorder that causes problems with both hearing and vision. People with this disorder have moderate to profound hearing loss in both ears that may worsen over time. The hearing loss may be described as sensorineural, meaning that it is related to changes in the inner ear, or it may be caused by auditory neuropathy, which is a problem with the transmission of sound (auditory) signals from the inner ear to the brain. The hearing loss is either present at birth (congenital) or begins in infancy, before the child learns to speak (prelingual).  Affected individuals also have severe nearsightedness (high myopia). These individuals are able to see nearby objects clearly, but objects that are farther away appear blurry. The myopia is usually diagnosed by early childhood.
Deafness and myopia syndrome is caused by mutations in the SLITRK6 gene. The protein produced from this gene is found primarily in the inner ear and the eye. This protein promotes growth and survival of nerve cells (neurons) in the inner ear that transmit auditory signals. It also controls (regulates) the growth of the eye after birth. In particular, the SLITRK6 protein influences the length of the eyeball (axial length), which affects whether a person will be nearsighted or farsighted, or will have normal vision. The SLITRK6 protein spans the cell membrane, where it is anchored in the proper position to perform its function.  SLITRK6 gene mutations that cause deafness and myopia syndrome result in an abnormally short SLITRK6 protein that is not anchored properly to the cell membrane. As a result, the protein is unable to function normally. Impaired SLITRK6 protein function leads to abnormal nerve development in the inner ear and improperly controlled eyeball growth, resulting in the hearing loss and nearsightedness that occur in deafness and myopia syndrome.
These resources address the diagnosis or management of deafness and myopia syndrome:  - Baby's First Test: Hearing Loss  - EyeSmart: Eyeglasses for Vision Correction  - Gene Review: Gene Review: Deafness and Myopia Syndrome  - Harvard Medical School Center for Hereditary Deafness  - KidsHealth: Hearing Evaluation in Children  - MedlinePlus Encyclopedia: Cochlear Implant  - MedlinePlus Health Topic: Cochlear Implants  - MedlinePlus Health Topic: Hearing Aids  - MedlinePlus Health Topic: Newborn Screening   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Primary sclerosing cholangitis is a condition that affects the bile ducts. These ducts carry bile (a fluid that helps to digest fats) from the liver, where bile is produced, to the gallbladder, where it is stored, and to the small intestine, where it aids in digestion. Primary sclerosing cholangitis occurs because of inflammation in the bile ducts (cholangitis) that leads to scarring (sclerosis) and narrowing of the ducts. As a result, bile cannot be released to the gallbladder and small intestine, and it builds up in the liver.  Primary sclerosing cholangitis is usually diagnosed around age 40, and for unknown reasons, it affects men twice as often as women. Many people have no signs or symptoms of the condition when they are diagnosed, but routine blood tests reveal liver problems. When apparent, the earliest signs and symptoms of primary sclerosing cholangitis include extreme tiredness (fatigue), discomfort in the abdomen, and severe itchiness (pruritus). As the condition worsens, affected individuals may develop yellowing of the skin and whites of the eyes (jaundice) and an enlarged spleen (splenomegaly). Eventually, the buildup of bile damages the liver cells, causing chronic liver disease (cirrhosis) and liver failure. Without bile available to digest them, fats pass through the body. As a result, weight loss and shortages of vitamins that are absorbed with and stored in fats (fat-soluble vitamins) can occur. A fat-soluble vitamin called vitamin D helps absorb calcium and helps bones harden, and lack of this vitamin can cause thinning of the bones (osteoporosis) in people with primary sclerosing cholangitis.  Primary sclerosing cholangitis is often associated with another condition called inflammatory bowel disease, which is characterized by inflammation of the intestines that causes open sores (ulcers) in the intestines and abdominal pain. However, the reason for this link is unclear. Approximately 70 percent of people with primary sclerosing cholangitis have inflammatory bowel disease, most commonly a form of the condition known as ulcerative colitis. In addition, people with primary sclerosing cholangitis are more likely to have an autoimmune disorder, such as type 1 diabetes, celiac disease, or thyroid disease, than people without the condition. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. People with primary sclerosing cholangitis also have an increased risk of developing cancer, particularly cancer of the bile ducts (cholangiocarcinoma).
Primary sclerosing cholangitis is thought to arise from a combination of genetic and environmental factors. Researchers believe that genetic changes play a role in this condition because it often occurs in several members of a family and because immediate family members of someone with primary sclerosing cholangitis have an increased risk of developing the condition. It is likely that specific genetic variations increase a person's risk of developing primary sclerosing cholangitis, and then exposure to certain environmental factors triggers the disorder. However, the genetic changes that increase susceptibility and the environmental triggers remain unclear.  There is evidence that variations in certain genes involved in immune function influence the risk of developing primary sclerosing cholangitis. The most commonly associated genes belong to a family of genes called the human leukocyte antigen (HLA) complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders (such as viruses and bacteria). Each HLA gene has many different normal variations, allowing each person's immune system to react to a wide range of foreign proteins. Specific variations of several HLA genes seem to be present more often in people with primary sclerosing cholangitis than in people who do not have the disorder. These variations may dysregulate the body's immune response, leading to the inflammation of the bile ducts in people with primary sclerosing cholangitis. However, the mechanism is not well understood. Researchers are also studying variations in other genes related to the body's immune function to understand how they contribute to the risk of developing this condition.
These resources address the diagnosis or management of primary sclerosing cholangitis:  - American Liver Foundation: Primary Sclerosing Cholangitis (PSC)  - Genetic Testing Registry: Primary sclerosing cholangitis  - MedlinePlus Encyclopedia: Sclerosing Cholangitis  - University of California San Francisco Medical Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is an inherited disorder that impairs the body's ability to break down ketones, which are molecules produced in the liver during the breakdown of fats.  The signs and symptoms of SCOT deficiency typically appear within the first few years of life. Affected individuals experience episodes of extreme tiredness (lethargy), appetite loss, vomiting, rapid breathing, and, occasionally, seizures. These episodes, which are called ketoacidotic attacks, sometimes lead to coma. About half of affected individuals have a ketoacidotic attack within the first 4 days of life. Affected individuals have no symptoms of the disorder between ketoacidotic attacks.  People with SCOT deficiency usually have a permanently elevated level of ketones in their blood (persistent ketosis). If the level of ketones gets too high, which can be brought on by infections, fevers, or periods without food (fasting), a ketoacidotic attack can occur. The frequency of ketoacidotic attacks varies among affected individuals.
Mutations in the OXCT1 gene cause SCOT deficiency. The OXCT1 gene provides instructions for making an enzyme called succinyl-CoA:3-ketoacid CoA transferase (SCOT). The SCOT enzyme is made in the energy-producing centers of cells (mitochondria). The enzyme plays a role in the breakdown of ketones, which are an important source of energy during fasting or when energy demands are increased, such as during illness or when exercising.  OXCT1 gene mutations result in the production of a SCOT enzyme with little or no function. A reduction in the amount of functional enzyme leads to an inability to break down ketones, resulting in decreased energy production and an elevated level of ketones in the blood. If these signs become severe, a ketoacidotic attack can occur. Individuals with mutations that create an enzyme with partial function are still prone to ketoacidotic attacks, but are less likely to have persistent ketosis.