bowang0911/MedQuAD huggingface dataset:
Osteogenesis imperfecta (OI) is a group of genetic disorders that mainly affect the bones. The term "osteogenesis imperfecta" means imperfect bone formation. People with this condition have bones that break easily, often from mild trauma or with no apparent cause. Multiple fractures are common, and in severe cases, can occur even before birth. Milder cases may involve only a few fractures over a person's lifetime.  There are at least eight recognized forms of osteogenesis imperfecta, designated type I through type VIII. The types can be distinguished by their signs and symptoms, although their characteristic features overlap. Type I is the mildest form of osteogenesis imperfecta and type II is the most severe; other types of this condition have signs and symptoms that fall somewhere between these two extremes. Increasingly, genetic factors are used to define the different forms of osteogenesis imperfecta.  The milder forms of osteogenesis imperfecta, including type I, are characterized by bone fractures during childhood and adolescence that often result from minor trauma. Fractures occur less frequently in adulthood. People with mild forms of the condition typically have a blue or grey tint to the part of the eye that is usually white (the sclera), and may develop hearing loss in adulthood. Affected individuals are usually of normal or near normal height.  Other types of osteogenesis imperfecta are more severe, causing frequent bone fractures that may begin before birth and result from little or no trauma. Additional features of these conditions can include blue sclerae, short stature, hearing loss, respiratory problems, and a disorder of tooth development called dentinogenesis imperfecta. The most severe forms of osteogenesis imperfecta, particularly type II, can include an abnormally small, fragile rib cage and underdeveloped lungs. Infants with these abnormalities have life-threatening problems with breathing and often die shortly after birth.
Mutations in the COL1A1, COL1A2, CRTAP, and P3H1 genes cause osteogenesis imperfecta.  Mutations in the COL1A1 and COL1A2 genes are responsible for more than 90 percent of all cases of osteogenesis imperfecta. These genes provide instructions for making proteins that are used to assemble type I collagen. This type of collagen is the most abundant protein in bone, skin, and other connective tissues that provide structure and strength to the body.  Most of the mutations that cause osteogenesis imperfecta type I occur in the COL1A1 gene. These genetic changes reduce the amount of type I collagen produced in the body, which causes bones to be brittle and to fracture easily. The mutations responsible for most cases of osteogenesis imperfecta types II, III, and IV occur in either the COL1A1 or COL1A2 gene. These mutations typically alter the structure of type I collagen molecules. A defect in the structure of type I collagen weakens connective tissues, particularly bone, resulting in the characteristic features of osteogenesis imperfecta.  Mutations in the CRTAP and P3H1 genes are responsible for rare, often severe cases of osteogenesis imperfecta. Cases caused by CRTAP mutations are usually classified as type VII; when P3H1 mutations underlie the condition, it is classified as type VIII. The proteins produced from these genes work together to process collagen into its mature form. Mutations in either gene disrupt the normal folding, assembly, and secretion of collagen molecules. These defects weaken connective tissues, leading to severe bone abnormalities and problems with growth.  In cases of osteogenesis imperfecta without identified mutations in one of the genes described above, the cause of the disorder is unknown. These cases include osteogenesis imperfecta types V and VI. Researchers are working to identify additional genes that may be responsible for these conditions.
Most cases of osteogenesis imperfecta have an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition. Many people with type I or type IV osteogenesis imperfecta inherit a mutation from a parent who has the disorder. Most infants with more severe forms of osteogenesis imperfecta (such as type II and type III) have no history of the condition in their family. In these infants, the condition is caused by new (sporadic) mutations in the COL1A1 or COL1A2 gene.  Less commonly, osteogenesis imperfecta has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means two copies of the gene in each cell are altered. The parents of a child with an autosomal recessive disorder typically are not affected, but each carry one copy of the altered gene. Some cases of osteogenesis imperfecta type III are autosomal recessive; these cases usually result from mutations in genes other than COL1A1 and COL1A2. When osteogenesis imperfecta is caused by mutations in the CRTAP or P3H1 gene, the condition also has an autosomal recessive pattern of inheritance.
These resources address the diagnosis or management of osteogenesis imperfecta:  - Gene Review: Gene Review: COL1A1/2-Related Osteogenesis Imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta  - Genetic Testing Registry: Osteogenesis imperfecta type 5  - Genetic Testing Registry: Osteogenesis imperfecta type 6  - Genetic Testing Registry: Osteogenesis imperfecta type 7  - Genetic Testing Registry: Osteogenesis imperfecta type 8  - Genetic Testing Registry: Osteogenesis imperfecta type I  - Genetic Testing Registry: Osteogenesis imperfecta type III  - Genetic Testing Registry: Osteogenesis imperfecta with normal sclerae, dominant form  - Genetic Testing Registry: Osteogenesis imperfecta, recessive perinatal lethal  - MedlinePlus Encyclopedia: Osteogenesis Imperfecta   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
Lung cancer is a disease in which certain cells in the lungs become abnormal and multiply uncontrollably to form a tumor. Lung cancer may or may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, breathing problems, trouble swallowing or speaking, blood in the mucus, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Lung cancer occurs most often in adults in their sixties or seventies. Most people who develop lung cancer have a history of long-term tobacco smoking; however, the condition can occur in people who have never smoked.  Lung cancer is generally divided into two types, small cell lung cancer and non-small cell lung cancer, based on the size of the affected cells when viewed under a microscope. Non-small cell lung cancer accounts for 85 percent of lung cancer, while small cell lung cancer accounts for the remaining 15 percent.  Small cell lung cancer grows quickly and often spreads to other tissues (metastasizes), most commonly to the adrenal glands (small hormone-producing glands located on top of each kidney), liver, brain, and bones. In more than half of cases, the small cell lung cancer has spread beyond the lung at the time of diagnosis. After diagnosis, most people with small cell lung cancer survive for about one year; less than seven percent survive 5 years.  Non-small cell lung cancer is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs (alveoli) located throughout the lungs. Squamous cell carcinoma arises from the squamous cells that line the passages leading from the windpipe to the lungs (bronchi). Large cell carcinoma describes non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. As the name suggests, the tumor cells are large when viewed under a microscope. The 5-year survival rate for people with non-small cell lung cancer is usually between 11 and 17 percent; it can be lower or higher depending on the subtype and stage of the cancer.
Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In nearly all cases of lung cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the lung. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in lung cancer cells.  Mutations in the EGFR and KRAS genes are estimated to be present in up to half of all lung cancer cases. These genes each provide instructions for making a protein that is embedded within the cell membrane. When these proteins are turned on (activated) by binding to other molecules, signaling pathways are triggered within cells that promote cell growth and division (proliferation).  Mutations in either the EGFR or KRAS gene lead to the production of a protein that is constantly turned on (constitutively activated). As a result, cells are signaled to constantly proliferate, leading to tumor formation. When these gene changes occur in cells in the lungs, lung cancer develops.  Mutations in many other genes have each been found in a small proportion of cases.  In addition to genetic changes, researchers have identified many personal and environmental factors that expose individuals to cancer-causing compounds (carcinogens) and increase the rate at which somatic mutations occur, contributing to a person's risk of developing lung cancer. The greatest risk factor is long-term tobacco smoking, which increases a person's risk of developing lung cancer 20-fold. Other risk factors include exposure to air pollution, radon, asbestos, or secondhand smoke; long-term use of hormone replacement therapy for menopause; and a history of lung disease such as tuberculosis, emphysema, or chronic bronchitis. A history of lung cancer in closely related family members is also an important risk factor; however, because relatives with lung cancer were likely smokers, it is unclear whether the increased risk of lung cancer is the result of genetic factors or exposure to secondhand smoke.
Most cases of lung cancer are not related to inherited gene changes. These cancers are associated with somatic mutations that occur only in certain cells in the lung.  When lung cancer is related to inherited gene changes, the cancer risk is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop lung cancer.
These resources address the diagnosis or management of lung cancer:  - Genetic Testing Registry: Lung cancer  - Genetic Testing Registry: Non-small cell lung cancer  - Lung Cancer Mutation Consortium: About Mutation Testing  - MedlinePlus Encyclopedia: Lung Cancer--Non-Small Cell  - MedlinePlus Encyclopedia: Lung Cancer--Small Cell  - National Cancer Institute: Drugs Approved for Lung Cancer  - National Cancer Institute: Non-Small Cell Lung Cancer Treatment  - National Cancer Institute: Small Cell Lung Cancer Treatment   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
Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, commonly known as CARASIL, is an inherited condition that causes stroke and other impairments.  Abnormalities affecting the brain and other parts of the nervous system become apparent in an affected person's twenties or thirties. Often, muscle stiffness (spasticity) in the legs and problems with walking are the first signs of the disorder. About half of affected individuals have a stroke or similar episode before age 40. As the disease progresses, most people with CARASIL also develop mood and personality changes, a decline in thinking ability (dementia), memory loss, and worsening problems with movement.  Other characteristic features of CARASIL include premature hair loss (alopecia) and attacks of low back pain. The hair loss often begins during adolescence and is limited to the scalp. Back pain, which develops in early to mid-adulthood, results from the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from one another.  The signs and symptoms of CARASIL worsen slowly with time. Over the course of several years, affected individuals become less able to control their emotions and communicate with others. They increasingly require help with personal care and other activities of daily living; after a few years, they become unable to care for themselves. Most affected individuals die within a decade after signs and symptoms first appear, although few people with the disease have survived for 20 to 30 years.
CARASIL is caused by mutations in the HTRA1 gene. This gene provides instructions for making an enzyme that is found in many of the body's organs and tissues. One of the major functions of the HTRA1 enzyme is to regulate signaling by proteins in the transforming growth factor-beta (TGF-) family. TGF- signaling is essential for many critical cell functions. It also plays an important role in the formation of new blood vessels (angiogenesis).  In people with CARASIL, mutations in the HTRA1 gene prevent the effective regulation of TGF- signaling. Researchers suspect that abnormally increased TGF- signaling alters the structure of small blood vessels, particularly in the brain. These blood vessel abnormalities (described as arteriopathy) greatly increase the risk of stroke and lead to the death of nerve cells (neurons) in many areas of the brain. Dysregulation of TGF- signaling may also underlie the hair loss and back pain seen in people with CARASIL, although the relationship between abnormal TGF- signaling and these features is less clear.
These resources address the diagnosis or management of CARASIL:  - Gene Review: Gene Review: CARASIL  - Genetic Testing Registry: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy   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
Galactosialidosis is a condition that affects many areas of the body. The three forms of galactosialidosis are distinguished by the age at which symptoms develop and the pattern of features.  The early infantile form of galactosialidosis is associated with extensive swelling caused by fluid accumulation before birth (hydrops fetalis), a soft out-pouching in the lower abdomen (an inguinal hernia), and an enlarged liver and spleen (hepatosplenomegaly). Additional features of this form include abnormal bone development (dysostosis multiplex) and distinctive facial features that are often described as "coarse." Some infants have an enlarged heart (cardiomegaly); an eye abnormality called a cherry-red spot, which can be identified with an eye examination; and kidney disease that can progress to kidney failure. Infants with this form usually are diagnosed between birth and 3 months; they typically live into late infancy.  The late infantile form of galactosialidosis shares some features with the early infantile form, although the signs and symptoms are somewhat less severe and begin later in infancy. This form is characterized by short stature, dysostosis multiplex, heart valve problems, hepatosplenomegaly, and "coarse" facial features. Other symptoms seen in some individuals with this type include intellectual disability, hearing loss, and a cherry-red spot. Children with this condition typically develop symptoms within the first year of life. The life expectancy of individuals with this type varies depending on the severity of symptoms.  The juvenile/adult form of galactosialidosis has signs and symptoms that are somewhat different than those of the other two types. This form is distinguished by difficulty coordinating movements (ataxia), muscle twitches (myoclonus), seizures, and progressive intellectual disability. People with this form typically also have dark red spots on the skin (angiokeratomas), abnormalities in the bones of the spine, "coarse" facial features, a cherry-red spot, vision loss, and hearing loss. The age at which symptoms begin to develop varies widely among affected individuals, but the average age is 16. This form is typically associated with a normal life expectancy.
Mutations in the CTSA gene cause all forms of galactosialidosis. The CTSA gene provides instructions for making a protein called cathepsin A, which is active in cellular compartments called lysosomes. These compartments contain enzymes that digest and recycle materials when they are no longer needed. Cathepsin A works together with two enzymes, neuraminidase 1 and beta-galactosidase, to form a protein complex. This complex breaks down sugar molecules (oligosaccharides) attached to certain proteins (glycoproteins) or fats (glycolipids). Cathepsin A is also found on the cell surface, where it forms a complex with neuraminidase 1 and a protein called elastin binding protein. Elastin binding protein plays a role in the formation of elastic fibers, a component of the connective tissues that form the body's supportive framework.  CTSA mutations interfere with the normal function of cathepsin A. Most mutations disrupt the protein structure of cathepsin A, impairing its ability to form complexes with neuraminidase 1, beta-galactosidase, and elastin binding protein. As a result, these other enzymes are not functional, or they break down prematurely.  Galactosialidosis belongs to a large family of lysosomal storage disorders, each caused by the deficiency of a specific lysosomal enzyme or protein. In galactosialidosis, impaired functioning of cathepsin A and other enzymes causes certain substances to accumulate in the lysosomes.
These resources address the diagnosis or management of galactosialidosis:  - Genetic Testing Registry: Combined deficiency of sialidase AND beta galactosidase  - MedlinePlus Encyclopedia: Hepatosplenomegaly (image)  - MedlinePlus Encyclopedia: Hydrops fetalis   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 sensory and autonomic neuropathy type IE (HSAN IE) is a disorder that affects the nervous system. Affected individuals have a gradual loss of intellectual function (dementia), typically beginning in their thirties. In some people with this disorder, changes in personality become apparent before problems with thinking skills.  People with HSAN IE also develop hearing loss that is caused by abnormalities in the inner ear (sensorineural hearing loss). The hearing loss gets worse over time and usually progresses to moderate or severe deafness between the ages of 20 and 35.  HSAN IE is characterized by impaired function of nerve cells called sensory neurons, which transmit information about sensations such as pain, temperature, and touch. Sensations in the feet and legs are particularly affected in people with HSAN IE. Gradual loss of sensation in the feet (peripheral neuropathy), which usually begins in adolescence or early adulthood, can lead to difficulty walking. Affected individuals may not be aware of injuries to their feet, which can lead to open sores and infections. If these complications are severe, amputation of the affected areas may be required.  HSAN IE is also characterized by a loss of the ability to sweat (sudomotor function), especially on the hands and feet. Sweating is a function of the autonomic nervous system, which also controls involuntary body functions such as heart rate, digestion, and breathing. These other autonomic functions are unaffected in people with HSAN IE.  The severity of the signs and symptoms of HSAN IE and their age of onset are variable, even within the same family.
HSAN IE is caused by mutations in the DNMT1 gene. This gene provides instructions for making an enzyme called DNA (cytosine-5)-methyltransferase 1. This enzyme is involved in DNA methylation, which is the addition of methyl groups, consisting of one carbon atom and three hydrogen atoms, to DNA molecules. In particular, the enzyme helps add methyl groups to DNA building blocks (nucleotides) called cytosines.  DNA methylation is important in many cellular functions. These include determining whether the instructions in a particular segment of DNA are carried out or suppressed (gene silencing), regulating reactions involving proteins and fats (lipids), and controlling the processing of chemicals that relay signals in the nervous system (neurotransmitters). DNA (cytosine-5)-methyltransferase 1 is active in the adult nervous system. Although its specific function is not well understood, the enzyme may help regulate nerve cell (neuron) maturation and specialization (differentiation), the ability of neurons to migrate where needed and connect with each other, and neuron survival.  DNMT1 gene mutations that cause HSAN IE reduce or eliminate the enzyme's methylation function, resulting in abnormalities in the maintenance of the neurons that make up the nervous system. However, it is not known how the mutations cause the specific signs and symptoms of HSAN IE.
These resources address the diagnosis or management of hereditary sensory and autonomic neuropathy type IE:  - Gene Review: Gene Review: DNMT1-Related Dementia, Deafness, and Sensory Neuropathy  - University of Chicago: Center for Peripheral Neuropathy   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
CAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with CAV3-related distal myopathy experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood. A bump or other sudden impact on the muscles, especially those in the forearms, may cause them to exhibit repetitive tensing (percussion-induced rapid contraction). The rapid contractions can continue for up to 30 seconds and may be painful. Overgrowth (hypertrophy) of the calf muscles can also occur in CAV3-related distal myopathy. The muscles closer to the center of the body (proximal muscles) such as the thighs and upper arms are normal in this condition.