Druvith/medqa1 huggingface dataset:
Question:  What are the genetic changes related to TK2-related mitochondrial DNA depletion syndrome, myopathic form ?
Answer: As the condition name suggests, mutations in the TK2 gene cause TK2-MDS. The TK2 gene provides instructions for making an enzyme called thymidine kinase 2 that functions within cell structures called mitochondria, which are found in all tissues. Mitochondria are involved in a wide variety of cellular activities, including energy production; chemical signaling; and regulation of cell growth, cell division, and cell death. Mitochondria contain their own genetic material, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Thymidine kinase 2 is involved in the production and maintenance of mtDNA. Specifically, this enzyme plays a role in recycling mtDNA building blocks (nucleotides) so that errors in mtDNA sequencing can be repaired and new mtDNA molecules can be produced.  Mutations in the TK2 gene reduce the production or activity of thymidine kinase 2. A decrease in enzyme activity impairs recycling of mtDNA nucleotides, causing a shortage of nucleotides available for the repair and production of mtDNA molecules. A reduction in the amount of mtDNA (known as mtDNA depletion) impairs mitochondrial function. Greater mtDNA depletion tends to cause more severe signs and symptoms. The muscle cells of people with TK2-MDS have very low amounts of mtDNA, ranging from 5 to 30 percent of normal. Other tissues can have 60 percent of normal to normal amounts of mtDNA.  It is unclear why TK2 gene mutations typically affect only muscle tissue, but the high energy demands of muscle cells may make them the most susceptible to cell death when mtDNA is lost and less energy is produced in cells. The brain and the liver also have high energy demands, which may explain why these organs are affected in severe cases of TK2-MDS.
Question:  Is TK2-related mitochondrial DNA depletion syndrome, myopathic form inherited ?
Answer: This condition 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.
Question:  What are the treatments for TK2-related mitochondrial DNA depletion syndrome, myopathic form ?
Answer: These resources address the diagnosis or management of TK2-related mitochondrial DNA depletion syndrome, myopathic form:  - Cincinnati Children's Hospital: Mitochondrial Diseases Program  - Gene Review: Gene Review: TK2-Related Mitochondrial DNA Depletion Syndrome, Myopathic Form   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
Question:  What is (are) Brooke-Spiegler syndrome ?
Answer: Brooke-Spiegler syndrome is a condition involving multiple skin tumors that develop from structures associated with the skin (skin appendages), such as sweat glands and hair follicles. People with Brooke-Spiegler syndrome may develop several types of tumors, including growths called spiradenomas, trichoepitheliomas, and cylindromas. Spiradenomas develop in sweat glands. Trichoepitheliomas arise from hair follicles. The origin of cylindromas has been unclear; while previously thought to derive from sweat glands, they are now generally believed to begin in hair follicles. The tumors associated with Brooke-Spiegler syndrome are generally noncancerous (benign), but occasionally they may become cancerous (malignant). Affected individuals are also at increased risk of developing tumors in tissues other than skin appendages, particularly benign or malignant tumors of the salivary glands.  People with Brooke-Spiegler syndrome typically begin developing tumors in early adulthood. The tumors are most often found on the head and neck. They grow larger and increase in number over time. In severe cases, the tumors may get in the way of the eyes, ears, nose, or mouth and affect vision, hearing, or other functions. The tumors can be disfiguring and may contribute to depression or other psychological problems. For reasons that are unclear, females with Brooke-Spiegler syndrome are often more severely affected than males.
Question:  How many people are affected by Brooke-Spiegler syndrome ?
Answer: Brooke-Spiegler syndrome is a rare disorder; its prevalence is unknown.
Question:  What are the genetic changes related to Brooke-Spiegler syndrome ?
Answer: Brooke-Spiegler syndrome is caused by mutations in the CYLD gene. This gene provides instructions for making a protein that helps regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related proteins that help protect cells from self-destruction (apoptosis) in response to certain signals. In regulating the action of nuclear factor-kappa-B, the CYLD protein allows cells to respond properly to signals to self-destruct when appropriate, such as when the cells become abnormal. By this mechanism, the CYLD protein acts as a tumor suppressor, which means that it helps prevent cells from growing and dividing too fast or in an uncontrolled way.  People with Brooke-Spiegler syndrome are born with a mutation in one of the two copies of the CYLD gene in each cell. This mutation prevents the cell from making functional CYLD protein from the altered copy of the gene. However, enough protein is usually produced from the other, normal copy of the gene to regulate cell growth effectively. For tumors to develop, a second mutation or deletion of genetic material involving the other copy of the CYLD gene must occur in certain cells during a person's lifetime.  When both copies of the CYLD gene are mutated in a particular cell, that cell cannot produce any functional CYLD protein. The loss of this protein allows the cell to grow and divide in an uncontrolled way to form a tumor. In people with Brooke-Spiegler syndrome, a second CYLD mutation typically occurs in multiple cells over an affected person's lifetime. The loss of CYLD protein in different types of cells in the skin leads to the growth of a variety of skin appendage tumors.  Some researchers consider Brooke-Spiegler syndrome and two related conditions called multiple familial trichoepithelioma and familial cylindromatosis, which are also caused by CYLD gene mutations, to be different forms of the same disorder. It is unclear why mutations in the CYLD gene cause different patterns of skin appendage tumors in each of these conditions, or why the tumors are generally confined to the skin in these disorders.
Question:  Is Brooke-Spiegler syndrome inherited ?
Answer: Susceptibility to Brooke-Spiegler syndrome has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell increases the risk of developing this condition. However, a second, non-inherited mutation is required for development of skin appendage tumors in this disorder.
Question:  What are the treatments for Brooke-Spiegler syndrome ?
Answer: These resources address the diagnosis or management of Brooke-Spiegler syndrome:  - Genetic Testing Registry: Spiegler-Brooke 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
Question:  What is (are) late-infantile neuronal ceroid lipofuscinosis ?
Answer: Late-infantile neuronal ceroid lipofuscinosis (NCL) is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin in late infancy or early childhood. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision impairment. Late-infantile NCL affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), progressive intellectual disability, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.  Late-infantile NCL is one of a group of NCLs (collectively called Batten disease) that affect the nervous system and typically cause progressive problems with vision, movement, and thinking ability. The different types of NCLs are distinguished by the age at which signs and symptoms first appear.
Question:  How many people are affected by late-infantile neuronal ceroid lipofuscinosis ?
Answer: The prevalence of late-infantile NCL is unknown. Collectively, all forms of NCL affect an estimated 1 in 100,000 individuals worldwide. NCLs are more common in Finland, where approximately 1 in 12,500 individuals are affected.
Question:  What are the genetic changes related to late-infantile neuronal ceroid lipofuscinosis ?
Answer: Mutations in the TPP1 gene cause most cases of late-infantile NCL. Mutations in the CLN5, CLN6, CLN8, MFSD8, and PPT1 genes each account for a small percentage of cases.  The TPP1 gene produces an enzyme called tripeptidyl peptidase 1. This enzyme is found in cell structures called lysosomes, which digest and recycle different types of molecules. Tripeptidyl peptidase 1 breaks down protein fragments, known as peptides, into their individual building blocks (amino acids).  The proteins produced from the other genes involved in this condition are active either in lysosomes or in another cell compartment called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein production, processing, and transport. Within these cell structures, the proteins largely play roles in the breakdown of other proteins or substances.  Mutations in the TPP1, CLN5, CLN6, CLN8, MFSD8, or PPT1 gene usually reduce the production or activity of the particular protein or enzyme made from the gene. In many cases, a reduction in functional protein or enzyme results in incomplete breakdown of certain proteins and other materials. These materials accumulate in the lysosome forming fatty substances called lipopigments. In some cases, it is unclear what causes the buildup of lipopigments. In late-infantile NCL, these accumulations occur in cells throughout the body, but neurons seem particularly vulnerable to damage caused by lipopigments and a decrease in specific protein function. The progressive death of cells in the brain and other tissues leads to the signs and symptoms of late-infantile NCL.
Question:  Is late-infantile neuronal ceroid lipofuscinosis inherited ?
Answer: This condition 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.
Question:  What are the treatments for late-infantile neuronal ceroid lipofuscinosis ?
Answer: These resources address the diagnosis or management of late-infantile neuronal ceroid lipofuscinosis:  - Gene Review: Gene Review: Neuronal Ceroid-Lipofuscinoses  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 5  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 6  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 7  - Genetic Testing Registry: Ceroid lipofuscinosis neuronal 8  - Genetic Testing Registry: Late-infantile neuronal ceroid lipofuscinosis  - Genetic Testing Registry: Neuronal ceroid lipofuscinosis   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
Question:  What is (are) ataxia neuropathy spectrum ?
Answer: Ataxia neuropathy spectrum is part of a group of conditions called the POLG-related disorders. The conditions in this group feature a range of similar signs and symptoms involving muscle-, nerve-, and brain-related functions. Ataxia neuropathy spectrum now includes the conditions previously called mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).  As the name implies, people with ataxia neuropathy spectrum typically have problems with coordination and balance (ataxia) and disturbances in nerve function (neuropathy). The neuropathy can be classified as sensory, motor, or a combination of the two (mixed). Sensory neuropathy causes numbness, tingling, or pain in the arms and legs, and motor neuropathy refers to disturbance in the nerves used for muscle movement.  Most people with ataxia neuropathy spectrum also have severe brain dysfunction (encephalopathy) and seizures. Some affected individuals have weakness of the external muscles of the eye (ophthalmoplegia), which leads to drooping eyelids (ptosis). Other signs and symptoms can include involuntary muscle twitches (myoclonus), liver disease, depression, migraine headaches, or blindness.
Question:  How many people are affected by ataxia neuropathy spectrum ?
Answer: The prevalence of ataxia neuropathy spectrum is unknown.
Question:  What are the genetic changes related to ataxia neuropathy spectrum ?
Answer: Ataxia neuropathy spectrum is caused by mutations in the POLG gene or, rarely, the C10orf2 gene.  The POLG gene provides instructions for making one part, the alpha subunit, of a protein called polymerase gamma (pol ). The C10orf2 gene provides instructions for making a protein called Twinkle. Pol  and Twinkle function in mitochondria, which are structures within cells that use oxygen to convert the energy from food into a form cells can use. Mitochondria each contain a small amount of DNA, known as mitochondrial DNA (mtDNA), which is essential for the normal function of these structures. Pol  and Twinkle are both integral to the process of DNA replication by which new copies of mtDNA are produced.  Mutated pol  or mutated Twinkle reduce mtDNA replication. Although the mechanisms are unknown, mutations in the POLG gene often result in fewer copies of mtDNA (mtDNA depletion), and mutations in the C10orf2 gene often result in deletions of large regions of mtDNA (mtDNA deletion). MtDNA depletion or deletion occurs most commonly in muscle, brain, or liver cells. MtDNA depletion causes a decrease in cellular energy, which could account for the signs and symptoms of ataxia neuropathy spectrum. It is unclear what role mtDNA deletions play in the signs and symptoms of the condition.
Question:  Is ataxia neuropathy spectrum inherited ?
Answer: Ataxia neuropathy spectrum can have different inheritance patterns depending on the associated gene.  Mutations in the POLG gene cause a form of the condition that 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.  Mutations in the C10orf2 gene cause a form of the condition that is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
Question:  What are the treatments for ataxia neuropathy spectrum ?
Answer: These resources address the diagnosis or management of ataxia neuropathy spectrum:  - Gene Review: Gene Review: POLG-Related Disorders  - Genetic Testing Registry: Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis  - National Ataxia Foundation: Gene Testing for Hereditary Ataxia  - United Mitochondrial Disease Foundation: Diagnosis of Mitochondrial Disease   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
Question:  What is (are) pilomatricoma ?
Answer: Pilomatricoma, also known as pilomatrixoma, is a type of noncancerous (benign) skin tumor associated with hair follicles. Hair follicles are specialized structures in the skin where hair growth occurs. Pilomatricomas occur most often on the head or neck, although they can also be found on the arms, torso, or legs. A pilomatricoma feels like a small, hard lump under the skin. This type of tumor grows relatively slowly and usually does not cause pain or other symptoms. Most affected individuals have a single tumor, although rarely multiple pilomatricomas can occur. If a pilomatricoma is removed surgically, it tends not to grow back (recur).  Most pilomatricomas occur in people under the age of 20. However, these tumors can also appear later in life. Almost all pilomatricomas are benign, but a very small percentage are cancerous (malignant). Unlike the benign form, the malignant version of this tumor (known as a pilomatrix carcinoma) occurs most often in middle age or late in life.  Pilomatricoma usually occurs without other signs or symptoms (isolated), but this type of tumor has also rarely been reported with inherited conditions. Disorders that can be associated with pilomatricoma include Gardner syndrome, which is characterized by multiple growths (polyps) and cancers of the colon and rectum; myotonic dystrophy, which is a form of muscular dystrophy; and Rubinstein-Taybi syndrome, which is a condition that affects many parts of the body and is associated with an increased risk of both benign and malignant tumors.
Question:  How many people are affected by pilomatricoma ?
Answer: Pilomatricoma is an uncommon tumor. The exact prevalence is unknown, but pilomatricoma probably accounts for less than 1 percent of all benign skin tumors.
Question:  What are the genetic changes related to pilomatricoma ?
Answer: Mutations in the CTNNB1 gene are found in almost all cases of isolated pilomatricoma. These mutations are somatic, which means they are acquired during a person's lifetime and are present only in tumor cells. Somatic mutations are not inherited.  The CTNNB1 gene provides instructions for making a protein called beta-catenin. This protein plays an important role in sticking cells together (cell adhesion) and in communication between cells. It is also involved in cell signaling as part of the WNT signaling pathway. This pathway promotes the growth and division (proliferation) of cells and helps determine the specialized functions a cell will have (differentiation). WNT signaling is involved in many aspects of development before birth, as well as the maintenance and repair of adult tissues.  Among its many activities, beta-catenin appears to be necessary for the normal function of hair follicles. This protein is active in cells that make up a part of the hair follicle known as the matrix. These cells divide and mature to form the different components of the hair follicle and the hair shaft. As matrix cells divide, the hair shaft is pushed upward and extends beyond the skin.  Mutations in the CTNNB1 gene lead to a version of beta-catenin that is always turned on (constitutively active). The overactive protein triggers matrix cells to divide too quickly and in an uncontrolled way, leading to the formation of a pilomatricoma.  Most pilomatrix carcinomas, the malignant version of pilomatricoma, also have somatic mutations in the CTNNB1 gene. It is unclear why some pilomatricomas are cancerous but most others are not.
Question:  Is pilomatricoma inherited ?
Answer: Most people with isolated pilomatricoma do not have any other affected family members. However, rare families with multiple affected members have been reported. In these cases, the inheritance pattern of the condition (if any) is unknown.
Question:  What are the treatments for pilomatricoma ?
Answer: These resources address the diagnosis or management of pilomatricoma:  - Genetic Testing Registry: Pilomatrixoma   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
Question:  What is (are) Tietz syndrome ?
Answer: Tietz syndrome is a disorder characterized by profound hearing loss from birth, fair skin, and light-colored hair. The hearing loss in affected individuals is caused by abnormalities of the inner ear (sensorineural hearing loss) and is present from birth. Although people with Tietz syndrome are born with white hair and very pale skin, their hair color often darkens over time to blond or red. The skin of affected individuals, which sunburns very easily, may tan slightly or develop reddish freckles with limited sun exposure; however, their skin and hair color remain lighter than those of other members of their family.  Tietz syndrome also affects the eyes. The colored part of the eye (the iris) in affected individuals is blue, and specialized cells in the eye called retinal pigment epithelial cells lack their normal pigment. The retinal pigment epithelium nourishes the retina, the part of the eye that detects light and color. The changes to the retinal pigment epithelium are generally detectable only by an eye examination; it is unclear whether the changes affect vision.
Question:  How many people are affected by Tietz syndrome ?
Answer: Tietz syndrome is a rare disorder; its exact prevalence is unknown. Only a few affected families have been described in the medical literature.
Question:  What are the genetic changes related to Tietz syndrome ?
Answer: Tietz syndrome is caused by mutations in the MITF gene. This gene provides instructions for making a protein that plays a role in the development, survival, and function of certain types of cells. Molecules of the MITF protein attach (bind) to each other or with other proteins that have a similar structure, creating a two-protein unit (dimer). The dimer attaches to specific areas of DNA and helps control the activity of particular genes. On the basis of this action, the MITF protein is called a transcription factor.  The MITF protein helps control the development and function of pigment-producing cells called melanocytes. Within these cells, this protein controls production of the pigment melanin, which contributes to hair, eye, and skin color. Melanocytes are also found in the inner ear and play an important role in hearing. Additionally, the MITF protein regulates the development of the retinal pigment epithelium.  MITF gene mutations that cause Tietz syndrome either delete or change a single protein building block (amino acid) in an area of the MITF protein known as the basic motif region. Dimers incorporating the abnormal MITF protein cannot be transported into the cell nucleus to bind with DNA. As a result, most of the dimers are unavailable to bind to DNA, which affects the development of melanocytes and the production of melanin. The resulting reduction or absence of melanocytes in the inner ear leads to hearing loss. Decreased melanin production (hypopigmentation) accounts for the light skin and hair color and the retinal pigment epithelium changes that are characteristic of Tietz syndrome.  Researchers suggest that Tietz syndrome may represent a severe form of a disorder called Waardenburg syndrome, which can also be caused by MITF gene mutations.
Question:  Is Tietz syndrome inherited ?
Answer: This condition 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.
Question:  What are the treatments for Tietz syndrome ?
Answer: These resources address the diagnosis or management of Tietz syndrome:  - Genetic Testing Registry: Tietz 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