bowang0911/MedQuAD huggingface dataset:
Mutations in the COL4A1 gene cause HANAC syndrome. The COL4A1 gene provides instructions for making one component of a protein called type IV collagen. Type IV collagen molecules attach to each other to form complex protein networks. These protein networks are the main component of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. Type IV collagen networks play an important role in the basement membranes in virtually all tissues throughout the body, particularly the basement membranes surrounding the body's blood vessels (vasculature).  The COL4A1 gene mutations that cause HANAC syndrome result in the production of a protein that disrupts the structure of type IV collagen. As a result, type IV collagen molecules cannot attach to each other to form the protein networks in basement membranes. Basement membranes without these networks are unstable, leading to weakening of the tissues that they surround. In people with HANAC syndrome, the vasculature and other tissues within the kidneys, brain, muscles, eyes, and throughout the body weaken.
These resources address the diagnosis or management of HANAC syndrome:  - Gene Review: Gene Review: COL4A1-Related Disorders  - Genetic Testing Registry: Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps   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
African iron overload is a condition that involves absorption of too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the liver, bone marrow, and spleen. Humans cannot increase the excretion of iron, although some iron is lost through bleeding or when cells of the intestine (enterocytes) are shed at the end of the cells' lifespan. Iron levels in the body are primarily regulated through control of how much iron is absorbed from the diet.  African iron overload results from a diet high in iron. It is particularly associated with consumption of a traditional African beer that contains dissolved iron from the metal drums in which it is brewed. Some evidence suggests that a genetic predisposition to absorbing too much iron may also be involved.  In African iron overload, excess iron typically accumulates in liver cells (hepatocytes) and certain immune cells called reticuloendothelial cells. Reticuloendothelial cells include macrophages in the bone marrow and spleen and Kuppfer cells, which are specialized macrophages found in the liver. Kuppfer cells and other macrophages help protect the body against foreign invaders such as viruses and bacteria.  When too much iron is absorbed, the resulting iron overload can eventually damage tissues and organs. Iron overload in the liver may lead to chronic liver disease (cirrhosis) in people with African iron overload. Cirrhosis increases the risk for developing a type of liver cancer called hepatocellular carcinoma. Iron overload in immune cells may affect their ability to fight infections. African iron overload is associated with an increased risk of developing infections such as tuberculosis.  People with African iron overload may have a slightly low number of red blood cells (mild anemia), possibly because the iron that accumulates in the liver, bone marrow, and spleen is less available for production of red blood cells. Affected individuals also have high levels of a protein called ferritin in their blood, which can be detected with a blood test. Ferritin stores and releases iron in cells, and cells produce more ferritin in response to excess amounts of iron.
African iron overload is common in rural areas of central and southern Africa; up to 10 percent of the population in these regions may be affected. Men seem to be affected more often than women, possibly due to some combination of differences in dietary iron consumption and gender differences in the processing of iron.  The prevalence of increased iron stores in people of African descent in other parts of the world is unknown; however, these individuals may be at higher risk of developing mildly increased iron stores than are people of European background.
African iron overload was first noted in rural central and southern African populations among people who drink a traditional beer brewed in uncoated steel drums that allow iron (a component of steel) to leach into the beer. However, not all individuals who drink the beer develop African iron overload, and not all individuals of African descent with iron overload drink the beer. Therefore, researchers are seeking genetic differences that affect the risk of developing this condition.  Some studies have indicated that a variation in the SLC40A1 gene increases the risk of developing increased iron stores in people of African descent. This variation is found in 5 to 20 percent of people of African descent but is not generally found in other populations.  The SLC40A1 gene provides instructions for making a protein called ferroportin. This protein is involved in the process of iron absorption in the body. Iron from the diet is absorbed through the walls of the small intestine. Ferroportin then transports iron from the small intestine into the bloodstream, and the iron is carried by the blood to the tissues and organs of the body. Ferroportin also transports iron out of reticuloendothelial cells in the liver, spleen, and bone marrow. The amount of iron absorbed by the body depends on the amount of iron stored and released from intestinal cells and macrophages.  The SLC40A1 gene variation that some studies have associated with increased iron stores in people of African descent may affect the way ferroportin helps to regulate iron absorption in the body. However, researchers suggest that this variation is not associated with most cases of African iron overload.
Hereditary multiple osteochondromas is a condition in which people develop multiple benign (noncancerous) bone tumors called osteochondromas. The number of osteochondromas and the bones on which they are located vary greatly among affected individuals. The osteochondromas are not present at birth, but approximately 96 percent of affected people develop multiple osteochondromas by the time they are 12 years old. Osteochondromas typically form at the end of long bones and on flat bones such as the hip and shoulder blade. Once people with hereditary multiple osteochondromas reach adult height and their bones stop growing, the development of new osteochondromas also usually stops.  Multiple osteochondromas can disrupt bone growth and can cause growth disturbances of the arms, hands, and legs, leading to short stature. Often these problems with bone growth do not affect the right and left limb equally, resulting in uneven limb lengths (limb length discrepancy). Bowing of the forearm or ankle and abnormal development of the hip joints (hip dysplasia) caused by osteochondromas can lead to difficulty walking and general discomfort. Multiple osteochondromas may also result in pain, limited range of joint movement, and pressure on nerves, blood vessels, the spinal cord, and tissues surrounding the osteochondromas.  Osteochondromas are typically benign; however, in some instances these tumors become malignant (cancerous). Researchers estimate that people with hereditary multiple osteochondromas have a 1 in 20 to 1 in 200 lifetime risk of developing cancerous osteochondromas (called sarcomas).
Mutations in the EXT1 and EXT2 genes cause hereditary multiple osteochondromas. The EXT1 gene and the EXT2 gene provide instructions for producing the proteins exostosin-1 and exostosin-2, respectively. The two exostosin proteins bind together and form a complex found in a cell structure called the Golgi apparatus, which modifies newly produced enzymes and other proteins. In the Golgi apparatus, the exostosin-1 and exostosin-2 complex modifies a protein called heparan sulfate so it can be used by the cell.  When there is a mutation in exostosin-1 or exostosin-2, heparan sulfate cannot be processed correctly and is nonfunctional. Although heparan sulfate is involved in many bodily processes, it is unclear how the lack of this protein contributes to the development of osteochondromas.  If the condition is caused by a mutation in the EXT1 gene it is called hereditary multiple osteochondromas type 1. A mutation in the EXT2 gene causes hereditary multiple osteochondromas type 2. While both type 1 and type 2 involve multiple osteochondromas, mutations in the EXT1 gene likely account for 55 to 75 percent of all cases of hereditary multiple osteochondromas, and the severity of symptoms associated with osteochondromas seems to be greater in type 1.  Researchers estimate that about 15 percent of people with hereditary multiple osteochondromas have no mutation in either the EXT1 or the EXT2 gene. It is not known why multiple osteochondromas form in these individuals.
These resources address the diagnosis or management of hereditary multiple osteochondromas:  - Gene Review: Gene Review: Hereditary Multiple Osteochondromas  - Genetic Testing Registry: Multiple congenital exostosis  - Genetic Testing Registry: Multiple exostoses type 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
Partington syndrome is a neurological disorder that causes intellectual disability along with a condition called focal dystonia that particularly affects movement of the hands. Partington syndrome usually occurs in males; when it occurs in females, the signs and symptoms are often less severe.  The intellectual disability associated with Partington syndrome usually ranges from mild to moderate. Some affected individuals have characteristics of autism spectrum disorders that affect communication and social interaction. Recurrent seizures (epilepsy) may also occur in Partington syndrome.  Focal dystonia of the hands is a feature that distinguishes Partington syndrome from other intellectual disability syndromes. Dystonias are a group of movement problems characterized by involuntary, sustained muscle contractions; tremors; and other uncontrolled movements. The term "focal" refers to a type of dystonia that affects a single part of the body, in this case the hands. In Partington syndrome, focal dystonia of the hands, which is called the Partington sign, begins in early childhood and gradually gets worse. This condition typically causes difficulty with grasping movements or using a pen or pencil.  People with Partington syndrome may also have dystonia affecting other parts of the body; dystonia affecting the muscles in the face and those involved in speech may cause impaired speech (dysarthria). People with this disorder may also have an awkward way of walking (gait). Signs and symptoms can vary widely, even within the same family.
Partington syndrome is caused by mutations in the ARX gene. This gene provides instructions for producing a protein that regulates the activity of other genes. Within the developing brain, the ARX protein is involved with movement (migration) and communication of nerve cells (neurons). In particular, this protein regulates genes that play a role in the migration of specialized neurons (interneurons) to their proper location. Interneurons relay signals between other neurons.  The normal ARX protein contains four regions where a protein building block (amino acid) called alanine is repeated multiple times. These stretches of alanines are known as polyalanine tracts. The most common mutation that causes Partington syndrome, a duplication of genetic material written as c.428_451dup, adds extra alanines to the second polyalanine tract in the ARX protein. This type of mutation is called a polyalanine repeat expansion. The expansion likely impairs ARX protein function and may disrupt normal interneuron migration in the developing brain, leading to the intellectual disability and dystonia characteristic of Partington syndrome.
This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. Females with one altered copy of the gene may have some signs and symptoms related to the condition. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
These resources address the diagnosis or management of Partington syndrome:  - American Academy of Child and Adolescent Psychiatry: Services in School for Children with Special Needs  - American Academy of Pediatrics: What is a Developmental/Behavioral Pediatrician?  - Centers for Disease Control and Prevention: Developmental Screening Fact Sheet  - Genetic Testing Registry: Partington X-linked mental retardation syndrome   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
Congenital deafness with labyrinthine aplasia, microtia, and microdontia (also called LAMM syndrome) is a condition that affects development of the ears and teeth. In people with this condition, the structures that form the inner ear are usually completely absent (labyrinthine aplasia). Rarely, affected individuals have some underdeveloped inner ear structures in one or both ears. The abnormalities of the inner ear cause a form of hearing loss called sensorineural deafness that is present from birth (congenital). Because the inner ear is important for balance as well as hearing, development of motor skills, such as sitting and crawling, may be delayed in affected infants. In addition, people with LAMM syndrome often have abnormally small outer ears (microtia) with narrow ear canals. They can also have unusually small, widely spaced teeth (microdontia).
LAMM syndrome is caused by mutations in the FGF3 gene, which provides instructions for making a protein called fibroblast growth factor 3 (FGF3). By attaching to another protein known as a receptor, the FGF3 protein triggers a cascade of chemical reactions inside the cell that signal the cell to undergo certain changes, such as dividing or maturing to take on specialized functions. During development before birth, the signals triggered by the FGF3 protein stimulate cells to form the structures that make up the inner ears. The FGF3 protein is also involved in the development of many other organs and structures, including the outer ears and teeth.  FGF3 gene mutations involved in LAMM syndrome alter the FGF3 protein. The altered protein likely has reduced or absent function and is unable to stimulate signaling. The loss of FGF3 function impairs development of the ears and teeth, which leads to the characteristic features of LAMM syndrome.
These resources address the diagnosis or management of LAMM syndrome:  - Gene Review: Gene Review: Congenital Deafness with Labyrinthine Aplasia, Microtia, and Microdontia  - Genetic Testing Registry: Deafness with labyrinthine aplasia microtia and microdontia (LAMM)   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
Myosin storage myopathy is a condition that causes muscle weakness (myopathy) that does not worsen or worsens very slowly over time. This condition is characterized by the formation of protein clumps, which contain a protein called myosin, within certain muscle fibers. The signs and symptoms of myosin storage myopathy usually become noticeable in childhood, although they can occur later. Because of muscle weakness, affected individuals may start walking later than usual and have a waddling gait, trouble climbing stairs, and difficulty lifting the arms above shoulder level. Muscle weakness also causes some affected individuals to have trouble breathing.
Mutations in the MYH7 gene cause myosin storage myopathy. The MYH7 gene provides instructions for making a protein known as the cardiac beta ()-myosin heavy chain. This protein is found in heart (cardiac) muscle and in type I skeletal muscle fibers, one of two types of fibers that make up the muscles that the body uses for movement. Cardiac -myosin heavy chain is the major component of the thick filament in muscle cell structures called sarcomeres. Sarcomeres, which are made up of thick and thin filaments, are the basic units of muscle contraction. The overlapping thick and thin filaments attach to each other and release, which allows the filaments to move relative to one another so that muscles can contract.  Mutations in the MYH7 gene lead to the production of an altered cardiac -myosin heavy chain protein, which is thought to be less able to form thick filaments. The altered proteins accumulate in type I skeletal muscle fibers, forming the protein clumps characteristic of the disorder. It is unclear how these changes lead to muscle weakness in people with myosin storage myopathy.
Citrullinemia is an inherited disorder that causes ammonia and other toxic substances to accumulate in the blood. Two forms of citrullinemia have been described; they have different signs and symptoms and are caused by mutations in different genes.  Type I citrullinemia (also known as classic citrullinemia) usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems are life-threatening in many cases. Less commonly, a milder form of type I citrullinemia can develop later in childhood or adulthood. This later-onset form is associated with intense headaches, partial loss of vision, problems with balance and muscle coordination (ataxia), and lethargy. Some people with gene mutations that cause type I citrullinemia never experience signs and symptoms of the disorder.  Type II citrullinemia chiefly affects the nervous system, causing confusion, restlessness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma. In some cases, the signs and symptoms of this disorder appear during adulthood (adult-onset). These signs and symptoms can be life-threatening, and are known to be triggered by certain medications, infections, surgery, and alcohol intake in people with adult-onset type II citrullinemia.  The features of adult-onset type II citrullinemia may also develop in people who as infants had a liver disorder called neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). This liver condition is also known as neonatal-onset type II citrullinemia. NICCD blocks the flow of bile (a digestive fluid produced by the liver) and prevents the body from processing certain nutrients properly. In many cases, the signs and symptoms of NICCD resolve within a year. Years or even decades later, however, some of these people develop the characteristic features of adult-onset type II citrullinemia.
Mutations in the ASS1 and SLC25A13 genes cause citrullinemia.  Citrullinemia belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of chemical reactions that takes place in liver cells. These reactions process excess nitrogen that is generated when protein is used by the body. The excess nitrogen is used to make a compound called urea, which is excreted in urine.  Mutations in the ASS1 gene cause type I citrullinemia. This gene provides instructions for making an enzyme, argininosuccinate synthase 1, that is responsible for one step of the urea cycle. Mutations in the ASS1 gene reduce the activity of the enzyme, which disrupts the urea cycle and prevents the body from processing nitrogen effectively. Excess nitrogen (in the form of ammonia) and other byproducts of the urea cycle accumulate in the bloodstream. Ammonia is particularly toxic to the nervous system, which helps explain the neurologic symptoms (such as lethargy, seizures, and ataxia) that are often seen in type I citrullinemia.  Mutations in the SLC25A13 gene are responsible for adult-onset type II citrullinemia and NICCD. This gene provides instructions for making a protein called citrin. Within cells, citrin helps transport molecules used in the production and breakdown of simple sugars, the production of proteins, and the urea cycle. Molecules transported by citrin are also involved in making nucleotides, which are the building blocks of DNA and its chemical cousin, RNA. Mutations in the SLC25A13 gene typically prevent cells from making any functional citrin, which inhibits the urea cycle and disrupts the production of proteins and nucleotides. The resulting buildup of ammonia and other toxic substances leads to the signs and symptoms of adult-onset type II citrullinemia. A lack of citrin also leads to the features of NICCD, although ammonia does not build up in the bloodstream of infants with this condition.
These resources address the diagnosis or management of citrullinemia:  - Baby's First Test: Citrullinemia, Type I  - Baby's First Test: Citrullinemia, Type II  - Gene Review: Gene Review: Citrin Deficiency  - Gene Review: Gene Review: Citrullinemia Type I  - Gene Review: Gene Review: Urea Cycle Disorders Overview  - Genetic Testing Registry: Citrullinemia type I  - Genetic Testing Registry: Citrullinemia type II  - Genetic Testing Registry: Neonatal intrahepatic cholestasis caused by citrin deficiency  - MedlinePlus Encyclopedia: Hereditary Urea Cycle Abnormality   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
Ophthalmo-acromelic syndrome is a condition that results in malformations of the eyes, hands, and feet. The features of this condition are present from birth. The eyes are often absent or severely underdeveloped (anophthalmia), or they may be abnormally small (microphthalmia). Usually both eyes are similarly affected in this condition, but if only one eye is small or missing, the other eye may have a defect such as a gap or split in its structures (coloboma).  The most common hand and foot malformation seen in ophthalmo-acromelic syndrome is missing fingers or toes (oligodactyly). Other frequent malformations include fingers or toes that are fused together (syndactyly) or extra fingers or toes (polydactyly). These skeletal malformations are often described as acromelic, meaning that they occur in the bones that are away from the center of the body. Additional skeletal abnormalities involving the long bones of the arms and legs or the spinal bones (vertebrae) can also occur. Affected individuals may have distinctive facial features, an opening in the lip (cleft lip) with or without an opening in the roof of the mouth (cleft palate), or intellectual disability.