bowang0911/MedQuAD huggingface dataset:
Mutations in the PNKD gene cause familial paroxysmal nonkinesigenic dyskinesia. The function of the protein produced from the PNKD gene is unknown; however, it is similar to a protein that helps break down a chemical called methylglyoxal. Methylglyoxal is found in alcoholic beverages, coffee, tea, and cola. Research has demonstrated that this chemical has a toxic effect on nerve cells (neurons). It remains unclear if the PNKD gene is related to the breakdown of methlglyoxal. How mutations in the PNKD gene lead to the signs and symptoms of familial paroxysmal nonkinesigenic dyskinesia is also unknown.
These resources address the diagnosis or management of familial paroxysmal nonkinesigenic dyskinesia:  - Gene Review: Gene Review: Familial Paroxysmal Nonkinesigenic Dyskinesia  - Genetic Testing Registry: Paroxysmal choreoathetosis  - Genetic Testing Registry: Paroxysmal nonkinesigenic dyskinesia 2   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
Mutations in the WFS1 gene cause more than 90 percent of Wolfram syndrome type 1 cases. This gene provides instructions for producing a protein called wolframin that is thought to regulate the amount of calcium in cells. A proper calcium balance is important for many different cellular functions, including cell-to-cell communication, the tensing (contraction) of muscles, and protein processing. The wolframin protein is found in many different tissues, such as the pancreas, brain, heart, bones, muscles, lung, liver, and kidneys. Within cells, wolframin is located in the membrane of a cell structure called the endoplasmic reticulum that is involved in protein production, processing, and transport. Wolframin's function is important in the pancreas, where the protein is thought to help process a protein called proinsulin into the mature hormone insulin. This hormone helps control blood sugar levels.  WFS1 gene mutations lead to the production of a wolframin protein that has reduced or absent function. As a result, calcium levels within cells are not regulated and the endoplasmic reticulum does not work correctly. When the endoplasmic reticulum does not have enough functional wolframin, the cell triggers its own cell death (apoptosis). The death of cells in the pancreas, specifically cells that make insulin (beta cells), causes diabetes mellitus in people with Wolfram syndrome. The gradual loss of cells along the optic nerve eventually leads to blindness in affected individuals. The death of cells in other body systems likely causes the various signs and symptoms of Wolfram syndrome type 1.  A certain mutation in the CISD2 gene was found to cause Wolfram syndrome type 2. The CISD2 gene provides instructions for making a protein that is located in the outer membrane of cell structures called mitochondria. Mitochondria are the energy-producing centers of cells. The exact function of the CISD2 protein is unknown, but it is thought to help keep mitochondria functioning normally.  The CISD2 gene mutation that causes Wolfram syndrome type 2 results in an abnormally small, nonfunctional CISD2 protein. As a result, mitochondria are not properly maintained, and they eventually break down. Since the mitochondria provide energy to cells, the loss of mitochondria results in decreased energy for cells. Cells that do not have enough energy to function will eventually die. Cells with high energy demands such as nerve cells in the brain, eye, or gastrointestinal tract are most susceptible to cell death due to reduced energy. It is unknown why people with CISD2 gene mutations have ulcers and bleeding problems in addition to the usual Wolfram syndrome features.  Some people with Wolfram syndrome do not have an identified mutation in either the WFS1 or CISD2 gene. The cause of the condition in these individuals is unknown.
When Wolfram syndrome is caused by mutations in the WFS1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Some studies have shown that people who carry one copy of a WFS1 gene mutation are at increased risk of developing individual features of Wolfram syndrome or related features, such as type 2 diabetes, hearing loss, or psychiatric illness. However, other studies have found no increased risk in these individuals.  Wolfram syndrome caused by mutations in the CISD2 gene is also inherited in an autosomal recessive pattern.
These resources address the diagnosis or management of Wolfram syndrome:  - Gene Review: Gene Review: WFS1-Related Disorders  - Genetic Testing Registry: Diabetes mellitus AND insipidus with optic atrophy AND deafness  - Genetic Testing Registry: Wolfram syndrome 2  - Johns Hopkins Medicine: Diabetes Insipidus  - MedlinePlus Encyclopedia: Diabetes Insipidus--Central  - Washington University, St. Louis: Wolfram Syndrome International Registry   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
Preeclampsia is a complication of pregnancy in which affected women develop high blood pressure (hypertension) and can also have abnormally high levels of protein in their urine. This condition usually occurs in the last few months of pregnancy and often requires the early delivery of the infant.  Many women with mild preeclampsia do not feel ill, and the problem is first detected through blood pressure and urine testing in their doctor's office. Other early features of the disorder are swelling (edema) of the face or hands and a weight gain of more than 2 pounds within a few days. More severely affected women may experience headaches, dizziness, irritability, shortness of breath, a decrease in urination, upper abdominal pain, nausea, or vomiting. Vision changes may develop, including flashing lights or spots, increased sensitivity to light (photophobia), blurry vision, or temporary blindness.  In most cases, preeclampsia is mild and goes away within a few weeks after the baby is born. In severe cases, however, preeclampsia can impact the mother's organs such as the heart, liver, and kidneys and can lead to life-threatening complications. Extreme hypertension in the mother can cause bleeding in the brain (hemorrhagic stroke). The effects of high blood pressure on the brain (hypertensive encephalopathy) may also result in seizures. If seizures occur, the condition is considered to have progressed to eclampsia, which can result in coma. Without treatment to help prevent seizures, about 1 in 200 women with preeclampsia develop eclampsia.  Between 10 and 20 percent of women with severe preeclampsia develop another potentially life-threatening complication called HELLP syndrome. HELLP stands for hemolysis (premature red blood cell breakdown), elevated liver enzyme levels, and low platelets (cell fragments involved in blood clotting), which are the key features of this condition.  Severe preeclampsia can also affect the fetus, with impairment of blood and oxygen flow leading to growth problems or stillbirth. Infants delivered early due to preeclampsia may have complications associated with prematurity, such as breathing problems caused by underdeveloped lungs.  Women who have had preeclampsia have approximately twice the lifetime risk of heart disease and stroke than do women in the general population. Researchers suggest this may be due to common factors that increase the risk of preeclampsia, heart disease, and stroke.
The specific causes of preeclampsia are not well understood. In pregnancy, blood volume normally increases to support the fetus, and the mother's body must adjust to handle this extra fluid. In some women the body does not react normally to the fluid changes of pregnancy, leading to the problems with high blood pressure and urine production in the kidneys that occur in preeclampsia.  The reasons for these abnormal reactions to the changes of pregnancy vary in different women and may differ depending on the stage of the pregnancy at which the condition develops. Studies suggest that preeclampsia is related to a problem with the placenta, the link between the mother's blood supply and the fetus. If there is an insufficient connection between the placenta and the arteries of the uterus, the placenta does not get enough blood. It responds by releasing a variety of substances, including molecules that affect the lining of blood vessels (the vascular endothelium). By mechanisms that are unclear, the reaction of the vascular endothelium appears to increase factors that cause the blood vessels to narrow (constrict), and decrease factors that would cause them to widen (dilate). As a result, the blood vessels constrict abnormally, causing hypertension. These blood vessel abnormalities also affect the kidneys, causing some proteins that are normally absorbed into the blood to be released in the urine instead.  Researchers are studying whether variations in genes involved in fluid balance, the functioning of the vascular endothelium, or placental development affect the risk of developing preeclampsia. Many other factors likely also contribute to the risk of developing this complex disorder. These risk factors include a first pregnancy; a pregnancy with twins or higher multiples; obesity; being older than 35 or younger than 20; a history of diabetes, hypertension, or kidney disease; and preeclampsia in a previous pregnancy. Socioeconomic status and ethnicity have also been associated with preeclampsia risk. The incidence of preeclampsia in the United States has increased by 30 percent in recent years, which has been attributed in part to an increase in older mothers and multiple births resulting from the use of assisted reproductive technologies.
These resources address the diagnosis or management of preeclampsia:  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: How Do Health Care Providers Diagnose Preeclampsia, Eclampsia, and HELLP syndrome?  - Eunice Kennedy Shriver National Institute of Child Health and Human Development: What Are the Treatments for Preeclampsia, Eclampsia, and HELLP Syndrome?  - Genetic Testing Registry: Preeclampsia/eclampsia 1  - Genetic Testing Registry: Preeclampsia/eclampsia 2  - Genetic Testing Registry: Preeclampsia/eclampsia 3  - Genetic Testing Registry: Preeclampsia/eclampsia 4  - Genetic Testing Registry: Preeclampsia/eclampsia 5  - MedlinePlus Encyclopedia: Preeclampsia Self-care   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
Ollier disease is a disorder characterized by multiple enchondromas, which are noncancerous (benign) growths of cartilage that develop within the bones. These growths most commonly occur in the limb bones, especially in the bones of the hands and feet; however, they may also occur in the skull, ribs, and bones of the spine (vertebrae). Enchondromas may result in severe bone deformities, shortening of the limbs, and fractures.  The signs and symptoms of Ollier disease may be detectable at birth, although they generally do not become apparent until around the age of 5. Enchondromas develop near the ends of bones, where normal growth occurs, and they frequently stop forming after affected individuals stop growing in early adulthood. As a result of the bone deformities associated with Ollier disease, people with this disorder generally have short stature and underdeveloped muscles.  Although the enchondromas associated with Ollier disease start out as benign, they may become cancerous (malignant). In particular, affected individuals may develop bone cancers called chondrosarcomas, especially in the skull. People with Ollier disease also have an increased risk of other cancers, such as ovarian or liver cancer.  People with Ollier disease usually have a normal lifespan, and intelligence is unaffected. The extent of their physical impairment depends on their individual skeletal deformities, but in most cases they have no major limitations in their activities.  A related disorder called Maffucci syndrome also involves multiple enchondromas but is distinguished by the presence of red or purplish growths in the skin consisting of tangles of abnormal blood vessels (hemangiomas).
In most people with Ollier disease, the disorder is caused by mutations in the IDH1 or IDH2 gene. These genes provide instructions for making enzymes called isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2, respectively. These enzymes convert a compound called isocitrate to another compound called 2-ketoglutarate. This reaction also produces a molecule called NADPH, which is necessary for many cellular processes. IDH1 or IDH2 gene mutations cause the enzyme produced from the respective gene to take on a new, abnormal function. Although these mutations have been found in some cells of enchondromas in people with Ollier disease, the relationship between the mutations and the signs and symptoms of the disorder is not well understood.  Mutations in other genes may also account for some cases of Ollier disease.
Ollier disease is not inherited. The mutations that cause this disorder are somatic, which means they occur during a person's lifetime. A somatic mutation occurs in a single cell. As that cell continues to grow and divide, the cells derived from it also have the same mutation. In Ollier disease, the mutation is thought to occur in a cell during early development before birth; cells that arise from that abnormal cell have the mutation, while the body's other cells do not. This situation is called mosaicism.
Autosomal recessive hypotrichosis is a condition that affects hair growth. People with this condition have sparse hair (hypotrichosis) on the scalp beginning in infancy. This hair is usually coarse, dry, and tightly curled (often described as woolly hair). Scalp hair may also be lighter in color than expected and is fragile and easily broken. Affected individuals often cannot grow hair longer than a few inches. The eyebrows, eyelashes, and other body hair may be sparse as well. Over time, the hair problems can remain stable or progress to complete scalp hair loss (alopecia) and a decrease in body hair.  Rarely, people with autosomal recessive hypotrichosis have skin problems affecting areas with sparse hair, such as redness (erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair growth, they may also develop bumps called hyperkeratotic follicular papules that develop around hair follicles, which are specialized structures in the skin where hair growth occurs.
Autosomal recessive hypotrichosis can be caused by mutations in the LIPH, LPAR6, or DSG4 gene. These genes provide instructions for making proteins that are involved in the growth and division (proliferation) and maturation (differentiation) of cells within hair follicles. These cell processes are important for the normal development of hair follicles and for hair growth; as the cells in the hair follicle divide, the hair strand (shaft) is pushed upward and extends beyond the skin, causing the hair to grow. The proteins produced from the LIPH, LPAR6, and DSG4 genes are also found in the outermost layer of skin (the epidermis) and glands in the skin that produce a substance that protects the skin and hair (sebaceous glands).  Mutations in the LIPH, LPAR6, or DSG4 gene result in the production of abnormal proteins that cannot aid in the development of hair follicles. As a result, hair follicles are structurally abnormal and often underdeveloped. Irregular hair follicles alter the structure and growth of hair shafts, leading to woolly, fragile hair that is easily broken. A lack of these proteins in the epidermis likely contributes to the skin problems sometimes seen in affected individuals.  In some areas of the body, other proteins can compensate for the function of the missing protein, so not all areas with hair are affected and not all individuals have skin problems.
Liddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.  In addition to hypertension, affected individuals can have low levels of potassium in the blood (hypokalemia). Signs and symptoms of hypokalemia include muscle weakness or pain, fatigue, constipation, or heart palpitations. The shortage of potassium can also raise the pH of the blood, a condition known as metabolic alkalosis.
Liddle syndrome is caused by mutations in the SCNN1B or SCNN1G gene. Each of these genes provides instructions for making a piece (subunit) of a protein complex called the epithelial sodium channel (ENaC). These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, where the channels transport sodium into cells.  In the kidney, ENaC channels open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine.  Mutations in the SCNN1B or SCNN1G gene change the structure of the respective ENaC subunit. The changes alter a region of the subunit that is involved in signaling for its breakdown (degradation) when it is no longer needed. As a result of the mutations, the subunit proteins are not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.
Familial male-limited precocious puberty is a condition that causes early sexual development in males; females are not affected. Boys with this disorder begin exhibiting the signs of puberty in early childhood, between the ages of 2 and 5. Signs of male puberty include a deepening voice, acne, increased body hair, underarm odor, growth of the penis and testes, and spontaneous erections. Changes in behavior, such as increased aggression and early interest in sex, may also occur. Without treatment, affected boys grow quickly at first, but they stop growing earlier than usual. As a result, they tend to be shorter in adulthood compared with other members of their family.
Familial male-limited precocious puberty can be caused by mutations in the LHCGR gene. This gene provides instructions for making a receptor protein called the luteinizing hormone/chorionic gonadotropin receptor. Receptor proteins have specific sites into which certain other proteins, called ligands, fit like keys into locks. Together, ligands and their receptors trigger signals that affect cell development and function.  The protein produced from the LHCGR gene acts as a receptor for two ligands: luteinizing hormone and a similar hormone called chorionic gonadotropin. The receptor allows the body to respond appropriately to these hormones. In males, chorionic gonadotropin stimulates the development of cells in the testes called Leydig cells, and luteinizing hormone triggers these cells to produce androgens. Androgens, including testosterone, are the hormones that control male sexual development and reproduction. In females, luteinizing hormone triggers the release of egg cells from the ovaries (ovulation); chorionic gonadotropin is produced during pregnancy and helps maintain conditions necessary for the pregnancy to continue.  Certain LHCGR gene mutations result in a receptor protein that is constantly turned on (constitutively activated), even when not attached (bound) to luteinizing hormone or chorionic gonadotropin. In males, the overactive receptor causes excess production of testosterone, which triggers male sexual development and lead to early puberty in affected individuals. The overactive receptor has no apparent effect on females.  Approximately 18 percent of individuals with familial male-limited precocious puberty have no identified LHCGR gene mutation. In these individuals, the cause of the disorder is unknown.
This condition is inherited in an autosomal dominant, male-limited pattern, which means one copy of the altered LHCGR gene in each cell is sufficient to cause the disorder in males. Females with mutations associated with familial male-limited precocious puberty appear to be unaffected. In some cases, an affected male inherits the mutation from either his mother or his father. Other cases result from new mutations in the gene and occur in males with no history of the disorder in their family.
These resources address the diagnosis or management of familial male-limited precocious puberty:  - Boston Children's Hospital: Precocious Puberty  - Genetic Testing Registry: Gonadotropin-independent familial sexual precocity   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
Pantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.  Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.  Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems.  A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration), which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.