bowang0911/MedQuAD huggingface dataset:
The mutation that causes acute promyelocytic leukemia involves two genes, the PML gene on chromosome 15 and the RARA gene on chromosome 17. A rearrangement of genetic material (translocation) between chromosomes 15 and 17, written as t(15;17), fuses part of the PML gene with part of the RARA gene. The protein produced from this fused gene is known as PML-RAR. This mutation is acquired during a person's lifetime and is present only in certain cells. This type of genetic change, called a somatic mutation, is not inherited.  The PML-RAR protein functions differently than the protein products of the normal PML and RARA genes. The protein produced from the RARA gene, RAR, is involved in the regulation of gene transcription, which is the first step in protein production. Specifically, this protein helps control the transcription of certain genes important in the maturation (differentiation) of white blood cells beyond the promyelocyte stage. The protein produced from the PML gene acts as a tumor suppressor, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. The PML-RAR protein interferes with the normal function of both the PML and the RAR proteins. As a result, blood cells are stuck at the promyelocyte stage, and they proliferate abnormally. Excess promyelocytes accumulate in the bone marrow and normal white blood cells cannot form, leading to acute promyelocytic leukemia.  The PML-RARA gene fusion accounts for up to 98 percent of cases of acute promyelocytic leukemia. Translocations involving the RARA gene and other genes have been identified in a few cases of acute promyelocytic leukemia.
These resources address the diagnosis or management of acute promyelocytic leukemia:  - American Cancer Society: Diagnosis of Acute Myeloid Leukemia  - American Cancer Society: Treatment of Acute Promyelocytic (M3) Leukemia  - Genetic Testing Registry: Acute promyelocytic leukemia  - MedlinePlus Encyclopedia: Acute Myeloid Leukemia  - National Cancer Institute: Adult Acute Myeloid Leukemia Treatment  - National Cancer Institute: Leukemia  - National Heart Lung and Blood Institute: Bone Marrow Tests   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
Horner syndrome is a disorder that affects the eye and surrounding tissues on one side of the face and results from paralysis of certain nerves. Horner syndrome can appear at any time of life; in about 5 percent of affected individuals, the disorder is present from birth (congenital).  Horner syndrome is characterized by drooping of the upper eyelid (ptosis) on the affected side, a constricted pupil in the affected eye (miosis) resulting in unequal pupil size (anisocoria), and absent sweating (anhidrosis) on the affected side of the face. Sinking of the eye into its cavity (enophthalmos) and a bloodshot eye often occur in this disorder. In people with Horner syndrome that occurs before the age of 2, the colored part (iris) of the eyes may differ in color (iris heterochromia), with the iris of the affected eye being lighter in color than that of the unaffected eye. Individuals who develop Horner syndrome after age 2 do not generally have iris heterochromia.  The abnormalities in the eye area related to Horner syndrome do not generally affect vision or health. However, the nerve damage that causes Horner syndrome may result from other health problems, some of which can be life-threatening.
Although congenital Horner syndrome can be passed down in families, no associated genes have been identified. Horner syndrome that appears after the newborn period (acquired Horner syndrome) and most cases of congenital Horner syndrome result from damage to nerves called the cervical sympathetics. These nerves belong to the part of the nervous system that controls involuntary functions (the autonomic nervous system). Within the autonomic nervous system, the nerves are part of a subdivision called the sympathetic nervous system. The cervical sympathetic nerves control several functions in the eye and face such as dilation of the pupil and sweating. Problems with the function of these nerves cause the signs and symptoms of Horner syndrome. Horner syndrome that occurs very early in life can lead to iris heterochromia because the development of the pigmentation (coloring) of the iris is under the control of the cervical sympathetic nerves.  Damage to the cervical sympathetic nerves can be caused by a direct injury to the nerves themselves, which can result from trauma that might occur during a difficult birth, surgery, or accidental injury. The nerves related to Horner syndrome can also be damaged by a benign or cancerous tumor, for example a childhood cancer of the nerve tissues called a neuroblastoma.  Horner syndrome can also be caused by problems with the artery that supplies blood to the head and neck (the carotid artery) on the affected side, resulting in loss of blood flow to the nerves. Some individuals with congenital Horner syndrome have a lack of development (agenesis) of the carotid artery. Tearing of the layers of the carotid artery wall (carotid artery dissection) can also lead to Horner syndrome.  The signs and symptoms of Horner syndrome can also occur during a migraine headache. When the headache is gone, the signs and symptoms of Horner syndrome usually also go away.  Some people with Horner syndrome have neither a known problem that would lead to nerve damage nor any history of the disorder in their family. These cases are referred to as idiopathic Horner syndrome.
Horner syndrome is usually not inherited and occurs in individuals with no history of the disorder in their family. Acquired Horner syndrome and most cases of congenital Horner syndrome have nongenetic causes. Rarely, congenital Horner syndrome is passed down within a family in a pattern that appears to be autosomal dominant, which means one copy of an altered gene in each cell is sufficient to cause the disorder. However, no genes associated with Horner syndrome have been identified.
Giant axonal neuropathy is an inherited condition involving dysfunction of a specific type of protein in nerve cells (neurons). The protein is essential for normal nerve function because it forms neurofilaments. Neurofilaments make up a structural framework that helps to define the shape and size of the neurons. This condition is characterized by abnormally large and dysfunctional axons, which are the specialized extensions of nerve cells that are required for the transmission of nerve impulses.  Giant axonal neuropathy generally appears in infancy or early childhood. It progresses slowly as neuronal injury becomes more severe. Signs of giant axonal neuropathy usually begin in the peripheral nervous system, which governs movement and sensation in the arms, legs, and other parts of the body. Most individuals with this disorder first have problems with walking. Later they may lose sensation, coordination, strength, and reflexes in their limbs. Hearing and visual problems may also occur. Extremely kinky hair (as compared to others in the family) is characteristic of giant axonal neuropathy, occurring in almost all affected people.  As the disorder progresses, the brain and spinal cord (central nervous system) may become involved, causing a gradual decline in mental function, loss of control of body movement, and seizures.
Giant axonal neuropathy is caused by mutations in the GAN gene, which provides instructions for making a protein called gigaxonin. Some GAN gene mutations change the shape of the protein, affecting how it binds to other proteins to form a functional complex. Other mutations prevent cells from producing any gigaxonin protein.  Gigaxonin is involved in a cellular function that destroys and gets rid of excess or damaged proteins using a mechanism called the ubiquitin-proteasome system. Neurons without functional gigaxonin accumulate excess neurofilaments in the axon, causing the axons to become distended. These giant axons do not transmit signals properly and eventually deteriorate, resulting in problems with movement and other nervous system dysfunction.
Familial hemophagocytic lymphohistiocytosis is a disorder in which the immune system produces too many activated immune cells (lymphocytes) called T cells, natural killer cells, B cells, and macrophages (histiocytes). Excessive amounts of immune system proteins called cytokines are also produced. This overactivation of the immune system causes fever and damages the liver and spleen, resulting in enlargement of these organs.  Familial hemophagocytic lymphohistiocytosis also destroys blood-producing cells in the bone marrow, a process called hemophagocytosis. As a result, affected individuals have low numbers of red blood cells (anemia) and a reduction in the number of blood cells involved in clotting (platelets). A reduction in platelets may cause easy bruising and abnormal bleeding.  The brain may also be affected in familial hemophagocytic lymphohistiocytosis. As a result, affected individuals may experience irritability, delayed closure of the bones of the skull in infants, neck stiffness, abnormal muscle tone, impaired muscle coordination, paralysis, blindness, seizures, and coma. In addition to neurological problems, familial hemophagocytic lymphohistiocytosis can cause abnormalities of the heart, kidneys, and other organs and tissues. Affected individuals also have an increased risk of developing cancers of blood-forming cells (leukemia and lymphoma).  Signs and symptoms of familial hemophagocytic lymphohistiocytosis usually become apparent during infancy, although occasionally they appear later in life. They usually occur when the immune system launches an exaggerated response to an infection, but may also occur in the absence of infection. Without treatment, most people with familial hemophagocytic lymphohistiocytosis survive only a few months.
Familial hemophagocytic lymphohistiocytosis may be caused by mutations in any of several genes. These genes provide instructions for making proteins that help destroy or deactivate lymphocytes that are no longer needed. By controlling the number of activated lymphocytes, these genes help regulate immune system function.  Approximately 40 to 60 percent of cases of familial hemophagocytic lymphohistiocytosis are caused by mutations in the PRF1 or UNC13D genes. Smaller numbers of cases are caused by mutations in other known genes. In some affected individuals, the genetic cause of the disorder is unknown.  The gene mutations that cause familial hemophagocytic lymphohistiocytosis impair the body's ability to regulate the immune system. These changes result in the exaggerated immune response characteristic of this condition.
These resources address the diagnosis or management of familial hemophagocytic lymphohistiocytosis:  - Gene Review: Gene Review: Hemophagocytic Lymphohistiocytosis, Familial  - Genetic Testing Registry: Familial hemophagocytic lymphohistiocytosis  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 2  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 3  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 4  - Genetic Testing Registry: Hemophagocytic lymphohistiocytosis, familial, 5  - The Merck Manual for Healthcare Professionals  - University of Minnesota: Pediatric Blood & Marrow Transplantation Center   These resources from MedlinePlus offer information about the diagnosis and management of various health conditions:  - Diagnostic Tests  - Drug Therapy  - Surgery and Rehabilitation  - Genetic Counseling   - Palliative Care
Dopamine transporter deficiency syndrome is a rare movement disorder. The condition is also known as infantile parkinsonism-dystonia because the problems with movement (dystonia and parkinsonism, described below) usually start in infancy and worsen over time. However, the features of the condition sometimes do not appear until childhood or later.  People with dopamine transporter deficiency syndrome develop a pattern of involuntary, sustained muscle contractions known as dystonia. The dystonia is widespread (generalized), affecting many different muscles. The continuous muscle cramping and spasms cause difficulty with basic activities, including speaking, eating, drinking, picking up objects, and walking.  As the condition worsens, affected individuals develop parkinsonism, which is a group of movement abnormalities including tremors, unusually slow movement (bradykinesia), rigidity, and an inability to hold the body upright and balanced (postural instability). Other signs and symptoms that can develop include abnormal eye movements; reduced facial expression (hypomimia); disturbed sleep; frequent episodes of pneumonia; and problems with the digestive system, including a backflow of acidic stomach contents into the esophagus (gastroesophageal reflux) and constipation.  People with dopamine transporter deficiency syndrome may have a shortened lifespan, although the long-term effects of this condition are not fully understood. Children with this condition have died from pneumonia and breathing problems. When the first signs and symptoms appear later in life, affected individuals may survive into adulthood.
Dopamine transporter deficiency syndrome is caused by mutations in the SLC6A3 gene. This gene provides instructions for making a protein called the dopamine transporter. This protein is embedded in the membrane of certain nerve cells (neurons) in the brain, where it transports a molecule called dopamine into the cell. Dopamine is a chemical messenger (neurotransmitter) that relays signals from one neuron to another. Dopamine has many important functions, including playing complex roles in thought (cognition), motivation, behavior, and control of movement.  Mutations in the SLC6A3 gene impair or eliminate the function of the dopamine transporter. The resulting shortage (deficiency) of functional transporter disrupts dopamine signaling in the brain. Although dopamine has a critical role in controlling movement, it is unclear how altered dopamine signaling causes the specific movement abnormalities found in people with dopamine transporter deficiency syndrome.  Studies suggest that the age at which signs and symptoms appear is related to how severely the function of the dopamine transporter is affected. Affected individuals who develop movement problems starting in infancy most often have transporter activity that is less than 5 percent of normal. Those whose movement problems appear in childhood or later tend to have somewhat higher levels of transporter activity, although they are still lower than normal. Researchers speculate that higher levels of transporter activity may delay the onset of the disease in these individuals.
Globozoospermia is a condition that affects only males. It is characterized by abnormal sperm and leads to an inability to father biological children (infertility).  Normal sperm cells have an oval-shaped head with a cap-like covering called the acrosome. The acrosome contains enzymes that break down the outer membrane of an egg cell, allowing the sperm to fertilize the egg. The sperm cells of males with globozoospermia, however, have a round head and no acrosome. The abnormal sperm are unable to fertilize an egg cell, leading to infertility.
Globozoospermia is most commonly caused by mutations in the DPY19L2 gene, which are found in about 70 percent of men with this condition. Mutations in other genes likely also cause globozoospermia.  The DPY19L2 gene provides instructions for making a protein that is found in developing sperm cells. The DPY19L2 protein is involved in the development of the acrosome and elongation of the sperm head, which are integral steps in sperm cell maturation. Mutations in the DPY19L2 gene result in a loss of functional DPY19L2 protein. As a result, sperm cells have no acrosome and do not elongate properly. Without an acrosome, the abnormal sperm are unable to get through the outer membrane of an egg cell to fertilize it, leading to infertility in affected men. Researchers have described other characteristics of the abnormal sperm cells that make fertilization of an egg cell difficult, although it is not clear how changes in the DPY19L2 gene are involved in development of these characteristics.
These resources address the diagnosis or management of globozoospermia:  - Association for Reproductive Medicine: Semen Analysis  - Centers for Disease Control: Assisted Reproductive Technology (ART)  - Genetic Testing Registry: Globozoospermia  - MedlinePlus Encyclopedia: Semen Analysis  - MedlinePlus Health Topic: Assisted Reproductive Technology   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
Recurrent hydatidiform mole occurs when women have at least two abnormal pregnancies described as hydatidiform moles. A hydatidiform mole occurs early in pregnancy when an embryo does not fully develop and the placenta develops abnormally. The placenta is a solid structure in the uterus that normally provides nutrients to a growing fetus. If a hydatidiform mole occurs once, it is known a sporadic hydatidiform mole; if it happens again, the condition is known as recurrent hydatidiform mole.  A hydatidiform mole often causes vaginal bleeding in the first trimester of the pregnancy. In an ultrasound examination, the abnormal placenta appears as numerous small sacs, often described as resembling a bunch of grapes. In some cases, the ultrasound shows no fetus, umbilical cord, or amniotic sac (a fluid-filled sac that normally surrounds the fetus).  Hydatidiform moles are not naturally discharged from the body and must be surgically removed, typically by the end of the first trimester. After removal, there is up to a 20 percent risk that any tissue left behind (persistent mole) will continue to grow and become a cancerous tumor called an invasive mole. The invasive mole can transform into a different form of cancer called gestational choriocarcinoma that can spread (metastasize) to other tissues such as the liver, lungs, or brain.
Mutations in the NLRP7 or KHDC3L gene can cause recurrent hydatidiform mole, with NLRP7 gene mutations being the most common cause.  Within egg cells (oocytes), both the NLRP7 and KHDC3L proteins are thought to play a role in turning off (inactivating) certain genes based on which parent the copy of the gene came from, a phenomenon known as genomic imprinting. For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. For a small subset of genes, however, only one of the two copies is active; for some of these genes, the copy from the father is normally active, while for others, the copy from the mother is normally active. The NLRP7 and KHDC3L proteins are likely involved in imprinting multiple maternal genes in oocytes, ensuring that they will be inactive in the developing embryo; the corresponding paternal genes are active.  NLRP7 or KHDC3L gene mutations result in the production of proteins with impaired function. As a result, multiple genes that contribute to a developing embryo are not imprinted properly, leading to abnormal gene activity (expression) in all pregnancies. Because many genes that would normally be inactive are instead active, embryonic development is impaired, resulting in a hydatidiform mole.  The NLRP7 protein has also been found to play a role in cell growth and division (proliferation) and cell maturation (differentiation). Research suggests that the NLRP7 protein plays an additional role in immune responses by regulating the release of an immune protein called interleukin-1 beta. Normally, the immune system would recognize a hydatidiform mole as a non-growing pregnancy or foreign tissue and signal the body to remove it. Because the impaired NLRP7 protein slows interleukin-1 beta release, the body cannot trigger an immune response to the abnormal pregnancy. Instead, the hydatidiform mole remains in the body. The cause of the retention of the pregnancy in women with KHDC3L gene mutations is unclear.  In some cases of recurrent hydatidiform mole, no mutations in either of these genes have been identified. In these instances, the cause of the condition is unknown.  When there is only a single instance of hydatidiform mole, it is often caused by abnormal fertilization of an egg. In sporadic hydatidiform mole, the embryo either receives genetic information only from sperm cells because the egg has no DNA-containing nucleus, or the embryo receives too much genetic information because two sperm cells fertilized one egg.
These resources address the diagnosis or management of recurrent hydatidiform mole:  - American Cancer Society: Signs and Symptoms of Gestational Trophoblastic Disease  - Genetic Testing Registry: Hydatidiform mole  - Genetic Testing Registry: Hydatidiform mole, recurrent, 2  - MedlinePlus Encyclopedia: Choriocarcinoma  - MedlinePlus Encyclopedia: Hydatidiform Mole   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
Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets.  People with CBF-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CBF-AML may include fever and weight loss.  While acute myeloid leukemia is generally a disease of older adults, CBF-AML often begins in young adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90 percent of individuals with CBF-AML recover from their disease following treatment, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, the disease recurs in approximately half of them after successful treatment of the initial occurrence.