bowang0911/MedQuAD huggingface dataset:
Mutations in the SRY gene have been identified in approximately 15 percent of individuals with Swyer syndrome. The SRY gene, located on the Y chromosome, provides instructions for making the sex-determining region Y protein. This protein is a transcription factor, which means it attaches (binds) to specific regions of DNA and helps control the activity of particular genes. The sex-determining region Y protein starts processes that are involved in male sexual development. These processes cause a fetus to develop male gonads (testes) and prevent the development of female reproductive structures (uterus and fallopian tubes). SRY gene mutations that cause Swyer syndrome prevent production of the sex-determining region Y protein or result in the production of a nonfunctioning protein. A fetus whose cells do not produce functional sex-determining region Y protein will not develop testes but will develop a uterus and fallopian tubes, despite having a typically male karyotype.  Swyer syndrome can also be caused by mutations in the MAP3K1 gene; research indicates that mutations in this gene may account for up to 18 percent of cases. The MAP3K1 gene provides instructions for making a protein that helps regulate signaling pathways that control various processes in the body. These include the processes of determining sexual characteristics before birth. The mutations in this gene that cause Swyer syndrome decrease signaling that leads to male sexual differentiation and enhance signaling that leads to female sexual differentiation, preventing the development of testes and allowing the development of a uterus and fallopian tubes.  Mutations in the DHH and NR5A1 genes have also been identified in small numbers of people with Swyer syndrome. The DHH gene provides instructions for making a protein that is important for early development of tissues in many parts of the body. The NR5A1 gene provides instructions for producing another transcription factor called the steroidogenic factor 1 (SF1). This protein helps control the activity of several genes related to the production of sex hormones and sexual differentiation. Mutations in the DHH and NR5A1 genes affect the process of sexual differentiation, preventing affected individuals with a typically male karyotype from developing testes and causing them to develop a uterus and fallopian tubes.  Changes affecting other genes have also been identified in a small number of people with Swyer syndrome. Nongenetic factors, such as hormonal medications taken by the mother during pregnancy, have also been associated with this condition. However, in most individuals with Swyer syndrome, the cause is unknown.
Most cases of Swyer syndrome are not inherited; they occur in people with no history of the condition in their family. These cases result either from nongenetic causes or from new (de novo) mutations in a gene that occur during the formation of reproductive cells (eggs or sperm) or in early embryonic development.  SRY-related Swyer syndrome is usually caused by a new mutation. However, some individuals with Swyer syndrome inherit an altered SRY gene from an unaffected father who is mosaic for the mutation. Mosaic means that an individual has the mutation in some cells (including some reproductive cells) but not in others. In rare cases, a father may carry the mutation in every cell of the body but also has other genetic variations that prevent him from being affected by the condition. Because the SRY gene is on the Y chromosome, Swyer syndrome caused by SRY gene mutations is described as having a Y-linked inheritance pattern.  When Swyer syndrome is associated with an MAP3K1 or NR5A1 gene mutation, the condition is also usually caused by a new mutation. In the rare inherited cases, the mutation may be inherited from either parent, since these genes are not on the Y chromosome. In these cases, the condition has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition.  Swyer syndrome caused by mutations in the DHH gene 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 are carriers of one copy of the altered gene. Female carriers of a DHH gene mutation generally have typical sex development. Male carriers of a DHH gene mutation may also be unaffected, or they may have genital differences such as the urethra opening on the underside of the penis (hypospadias).
These resources address the diagnosis or management of Swyer syndrome:  - Gene Review: Gene Review: 46,XY Disorder of Sex Development and 46,XY Complete Gonadal Dysgenesis  - Genetic Testing Registry: Pure gonadal dysgenesis 46,XY  - MedlinePlus Encyclopedia: Intersex  - University College London Hospitals: Disorders of Sexual Development   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
Spastic paraplegia type 11 is part of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia). Hereditary spastic paraplegias are divided into two types: pure and complex. The pure types involve the lower limbs. The complex types involve the lower limbs and can affect the upper limbs to a lesser degree. Complex spastic paraplegias also affect the structure or functioning of the brain and the peripheral nervous system, which consists of nerves connecting the brain and spinal cord to muscles and sensory cells that detect sensations such as touch, pain, heat, and sound. Spastic paraplegia type 11 is a complex hereditary spastic paraplegia.  Like all hereditary spastic paraplegias, spastic paraplegia type 11 involves spasticity of the leg muscles and muscle weakness. In almost all individuals with this type of spastic paraplegia, the tissue connecting the left and right halves of the brain (corpus callosum) is abnormally thin. People with this form of spastic paraplegia can also experience numbness, tingling, or pain in the arms and legs (sensory neuropathy); disturbance in the nerves used for muscle movement (motor neuropathy); intellectual disability; exaggerated reflexes (hyperreflexia) of the lower limbs; speech difficulties (dysarthria); reduced bladder control; and muscle wasting (amyotrophy). Less common features include difficulty swallowing (dysphagia), high-arched feet (pes cavus), an abnormal curvature of the spine (scoliosis), and involuntary movements of the eyes (nystagmus). The onset of symptoms varies greatly; however, abnormalities in muscle tone and difficulty walking usually become noticeable in adolescence.  Many features of spastic paraplegia type 11 are progressive. Most people experience a decline in intellectual ability and an increase in muscle weakness and nerve abnormalities over time. As the condition progresses, some people require wheelchair assistance.
Mutations in the SPG11 gene cause spastic paraplegia type 11. The SPG11 gene provides instructions for making the protein spatacsin. Spatacsin is active (expressed) throughout the nervous system, although its exact function is unknown. Researchers speculate that spatacsin may be involved in the maintenance of axons, which are specialized extensions of nerve cells (neurons) that transmit impulses throughout the nervous system.  SPG11 gene mutations typically change the structure of the spatacsin protein. The effect that the altered spatacsin protein has on the nervous system is not known. Researchers suggest that mutations in spatacsin may cause the signs and symptoms of spastic paraplegia type 11 by interfering with the protein's proposed role in the maintenance of axons.
These resources address the diagnosis or management of spastic paraplegia type 11:  - Gene Review: Gene Review: Spastic Paraplegia 11  - Genetic Testing Registry: Spastic paraplegia 11, autosomal recessive  - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies   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
Paroxysmal extreme pain disorder is a condition characterized by skin redness and warmth (flushing) and attacks of severe pain in various parts of the body. The area of flushing typically corresponds to the site of the pain. The pain attacks experienced by people with paroxysmal extreme pain disorder usually last seconds to minutes, but in some cases can last hours. These attacks can start as early as infancy. Early in life, the pain is typically concentrated in the lower part of the body, especially around the rectum, and is usually triggered by a bowel movement. Some children may develop constipation, which is thought to be due to fear of triggering a pain attack. Pain attacks in these young children may also be accompanied by seizures, slow heartbeat, or short pauses in breathing (apnea).  As a person with paroxysmal extreme pain disorder ages, the location of pain changes. Pain attacks switch from affecting the lower body to affecting the head and face, especially the eyes and jaw. Triggers of these pain attacks include changes in temperature (such as a cold wind) and emotional distress as well as eating spicy foods and drinking cold drinks.  Paroxysmal extreme pain disorder is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch, smell, and pain.
Mutations in the SCN9A gene cause paroxysmal extreme pain disorder. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels transport positively charged sodium atoms (sodium ions) into cells and play a key role in a cell's ability to generate and transmit electrical signals. NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.  The SCN9A gene mutations that cause paroxysmal extreme pain disorder result in NaV1.7 sodium channels that do not close completely when it is turned off, allowing sodium ions to flow abnormally into nociceptors. This increase in sodium ions enhances transmission of pain signals, leading to the pain attacks experienced by people with paroxysmal extreme pain disorder. It is unknown why the pain attacks associated with this condition change location over time or what causes the other features of this condition such as seizures and changes in breathing.
Multicentric osteolysis, nodulosis, and arthropathy (MONA) describes a rare inherited disease characterized by a loss of bone tissue (osteolysis), particularly in the hands and feet. MONA includes a condition formerly called nodulosis-arthropathy-osteolysis (NAO) syndrome. It may also include a similar disorder called Torg syndrome, although it is unknown whether Torg syndrome is actually part of MONA or a separate disorder caused by a mutation in a different gene.  In most cases of MONA, bone loss begins in the hands and feet, causing pain and limiting movement. Bone abnormalities can later spread to other areas of the body, with joint problems (arthropathy) occurring in the elbows, shoulders, knees, hips, and spine. Most people with MONA develop low bone mineral density (osteopenia) and thinning of the bones (osteoporosis) throughout the skeleton. These abnormalities make bones brittle and more prone to fracture. The bone abnormalities also lead to short stature.  Many affected individuals develop subcutaneous nodules, which are firm lumps of noncancerous tissue underneath the skin, especially on the soles of the feet. Some affected individuals also have skin abnormalities including patches of dark, thick, and leathery skin. Other features of MONA can include clouding of the clear front covering of the eye (corneal opacity), excess hair growth (hypertrichosis), overgrowth of the gums, heart abnormalities, and distinctive facial features that are described as "coarse."
MONA results from mutations in the MMP2 gene. This gene provides instructions for making an enzyme called matrix metallopeptidase 2, whose primary function is to cut (cleave) a protein called type IV collagen. Type IV collagen is a major structural component of basement membranes, which are thin, sheet-like structures that separate and support cells in many tissues. The activity of matrix metallopeptidase 2 appears to be important for a variety of body functions, including bone remodeling, which is a normal process in which old bone is broken down and new bone is created to replace it.  The MMP2 gene mutations that cause MONA completely eliminate the activity of the matrix metallopeptidase 2 enzyme, preventing the normal cleavage of type IV collagen. It is unclear how a loss of enzyme activity leads to the specific features of MONA. Researchers suspect that it somehow disrupts the balance of new bone creation and the breakdown of existing bone during bone remodeling, resulting in a progressive loss of bone tissue. How a shortage of matrix metallopeptidase 2 leads to the other features of MONA, such as subcutaneous nodules and skin abnormalities, is unknown.
Histidinemia is an inherited condition characterized by elevated blood levels of the amino acid histidine, a building block of most proteins. Histidinemia is caused by the shortage (deficiency) of the enzyme that breaks down histidine. Histidinemia typically causes no health problems, and most people with elevated histidine levels are unaware that they have this condition.  The combination of histidinemia and a medical complication during or soon after birth (such as a temporary lack of oxygen) might increase a person's chances of developing intellectual disability, behavioral problems, or learning disorders.
Histidinemia is caused by mutations in the HAL gene, which provides instructions for making an enzyme called histidase. Histidase breaks down histidine to a molecule called urocanic acid. Histidase is active (expressed) primarily in the liver and the skin.  HAL gene mutations lead to the production of a histidase enzyme that cannot break down histidine, which results in elevated levels of histidine in the blood and urine. These increased levels of histidine do not appear to have any negative effects on the body.
Myotonia congenita is a disorder that affects muscles used for movement (skeletal muscles). Beginning in childhood, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing normally. Although myotonia can affect any skeletal muscles, including muscles of the face and tongue, it occurs most often in the legs. Myotonia causes muscle stiffness that can interfere with movement. In some people the stiffness is very mild, while in other cases it may be severe enough to interfere with walking, running, and other activities of daily life. These muscle problems are particularly noticeable during movement following a period of rest. Many affected individuals find that repeated movements can temporarily alleviate their muscle stiffness, a phenomenon known as the warm-up effect.  The two major types of myotonia congenita are known as Thomsen disease and Becker disease. These conditions are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe muscle stiffness, particularly in males. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not seen in people with Thomsen disease.
Mutations in the CLCN1 gene cause myotonia congenita.  The CLCN1 gene provides instructions for making a protein that is critical for the normal function of skeletal muscle cells. For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contraction and relaxation are controlled by the flow of charged atoms (ions) into and out of muscle cells. Specifically, the protein produced from the CLCN1 gene forms a channel that controls the flow of negatively charged chlorine atoms (chloride ions) into these cells. The main function of this channel is to stabilize the cells' electrical charge, which prevents muscles from contracting abnormally.  Mutations in the CLCN1 gene alter the usual structure or function of chloride channels. The altered channels cannot properly regulate ion flow, reducing the movement of chloride ions into skeletal muscle cells. This disruption in chloride ion flow triggers prolonged muscle contractions, which are the hallmark of myotonia.
The two forms of myotonia congenita have different patterns of inheritance. Thomsen disease 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, an affected person has one parent with the condition.  Becker disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition.  Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita.
These resources address the diagnosis or management of myotonia congenita:  - Gene Review: Gene Review: Myotonia Congenita  - Genetic Testing Registry: Congenital myotonia, autosomal dominant form  - Genetic Testing Registry: Congenital myotonia, autosomal recessive form  - Genetic Testing Registry: Myotonia congenita  - MedlinePlus Encyclopedia: Myotonia congenita   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
Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).  Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.  In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.  Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder.
Mutations in any of three genes, ETFA, ETFB, and ETFDH, can result in glutaric acidemia type II. The ETFA and ETFB genes provide instructions for producing two protein segments, or subunits, that come together to make an enzyme called electron transfer flavoprotein. The ETFDH gene provides instructions for making another enzyme called electron transfer flavoprotein dehydrogenase.  Glutaric acidemia type II is caused by a deficiency in either of these two enzymes. Electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase are normally active in the mitochondria, which are the energy-producing centers of cells. These enzymes help break down proteins and fats to provide energy for the body. When one of the enzymes is defective or missing, partially broken down nutrients accumulate in the cells and damage them, causing the signs and symptoms of glutaric acidemia type II.  People with mutations that result in a complete loss of either enzyme produced from the ETFA, ETFB or ETFDH genes are likely to experience the most severe symptoms of glutaric acidemia type II. Mutations that allow the enzyme to retain some activity may result in milder forms of the disorder.
Atelosteogenesis type 2 is a severe disorder of cartilage and bone development. Infants born with this condition have very short arms and legs, a narrow chest, and a prominent, rounded abdomen. This disorder is also characterized by an opening in the roof of the mouth (a cleft palate), distinctive facial features, an inward- and upward-turning foot (clubfoot), and unusually positioned thumbs (hitchhiker thumbs).  The signs and symptoms of atelosteogenesis type 2 are similar to those of another skeletal disorder called diastrophic dysplasia; however, atelosteogenesis type 2 is typically more severe. As a result of serious health problems, infants with this disorder are usually stillborn or die soon after birth from respiratory failure. Some infants, however, have lived for a short time with intensive medical support.
Atelosteogenesis type 2 is one of several skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Cartilage is a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Mutations in the SLC26A2 gene disrupt the structure of developing cartilage, preventing bones from forming properly and resulting in the skeletal problems characteristic of atelosteogenesis type 2.
These resources address the diagnosis or management of atelosteogenesis type 2:  - Gene Review: Gene Review: Atelosteogenesis Type 2  - Genetic Testing Registry: Atelosteogenesis 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