| Allele | a version of gene; a person inherits two alleles for each gene, one from each parent. | 4H patients inherit two alleles that have pathogenic variants in them causing 4H leukodystrophy | Homozygous, Heterozygous | https://www.youtube.com/watch?v=FsaYSGWuRmo&ab_channel=StatedClearly |
| Alternative splicing | the same messenger RNA can be spliced in different ways, yielding different proteins from the same gene | Some variants might cause alternative splicing in a 4H patient, meaning they produce some normal messenger RNA and some that is atypical | Splicing, RNA, protein | https://www.youtube.com/watch?v=xZwSmUNRBQQ&ab_channel=BiologyProfessor |
| Ambulatory | able to walk | Some 4H patients may never be ambulatory or may lose the ability to walk as the disease progresses | Regression | https://www.verywellhealth.com/what-is-ambulatory-2615114 |
| Amino acid | the building blocks of proteins | Many 4H patients have variants that cause an amino acid to be substituted in the resulting protein chain | Protein, Missense | https://www.technologynetworks.com/applied-sciences/articles/essential-amino-acids-chart-abbreviations-and-structure-324357 |
| Ataxia | diffculty with balance and coordination | Ataxia is a common symptom of 4H leukodystrophy; falls should be avoided as much as possible | Tremor, Dysmetria | https://www.youtube.com/watch?v=Ri5iUR4Pi_0&ab_channel=Medskl.com |
| Autosomal recessive | a certain way a condition can be passed down in families where both copies of the gene must be changed to be affected with the condition | 4H leukodystrophy is an autosomal recessive condition | Biallelic, Homozygous, Compound Heterozygous | https://www.geneticsupport.org/genetics-101/inheritance-patterns/autosomal-recessive/ |
| Axon (Nerve fibre) | the long, cable-like part of the neuron that carries electrical impulses away from the cell body | Because individuals with 4H don’t make enough myelin during development, the electrical impulses sent through their axons are slower | Myelin, Myelination, Neuron | https://askabiologist.asu.edu/sites/default/files/resources/articles/neuron_anatomy.jpg |
| Basal ganglia | a group of structures deep within the brain that help start and control movement | Individuals with a more severe form of 4H leukodystrophy may have abnormalities of the basal ganglia, as seen on MRI | MRI, Thalamus, Cerebellar atrophy, Hypomyelination | https://www.youtube.com/watch?v=OD2KPSGZ1No&ab_channel=NeuroscientificallyChallenged |
| Biallelic | referring to both alleles, or copies, of a gene | 4H patients have biallelic pathogenic variants, meaning changes (not necessarily identical changes) are present in both copies of the gene | Homozygous, Compound heterozygous, Autosomal recessive | |
| Carrier | a person who carries and could pass on a genetic change associated with an autosomal recessive condition, but is healthy and unaffected | Parents of children with 4H leukodystrophy are carriers of the condition. Unaffected siblings and other family members may also be carriers. | Heterozygous, Autosomal recessive, Carrier frequency | https://www.genome.gov/genetics-glossary/Carrier |
| Carrier frequency | the proportion of people in a population who have a pathogenic variant in one copy of the gene, “carriers” | For example, the carrier frequency for the c.1568T pathogenic variant in POLR3B is estimated to be 0.5% | Carrier, Heterozygous | |
| Cell therapy | the transplantation of human cells, especially stem cells or induced pluriopotenet stem cells, to treat disease | Intracerebral stem cell therapy (administered into the brain) is a potential future avenue for treatment of 4H leukodystrophy | Induced pluripotent stem cells (iPSC), Gene therapy, Gene editing, Clinical trials | https://www.youtube.com/watch?v=aO4-KFEz8NE&ab_channel=ASGCT |
| Central dogma | the flow of genetic information from DNA to protein | The central dogma includes transcription and translation, important processes for expressing genes, including genes associated with 4H leukodystrophy | Transcription, Translation, Gene | https://www.youtube.com/watch?v=zwibgNGe4aY&ab_channel=StatedClearly |
| Cerebellar atrophy | shrinkage of the part of the brain that controls coordination and motor learning | Cerebellar atrophy is often seen on brain MRI for 4H patients and may cause features like ataxia, dysmetria, dysarthria, and tremor | Magnetic Resonance Imaging (MRI), Ataxia, Dysmetria, Dysarthria, Tremor | https://youtu.be/DIeUvYknB_E?t=705 |
| Chromosome | a tightly coiled strand of DNA containing a specific set of genes; we have 23 pairs of chromosomes, inheriting one set from each parent for 46 total | The genes associated with 4H leukodystrophy are located and passed down on chromosomes | DNA, Gene, Variant | https://www.youtube.com/watch?v=IePMXxQ-KWY&ab_channel=StatedClearly |
| Clinical trial | research studies involving human subjects that are done to test whether a treatment is safe and effective | Future treatments for 4H leukodystrophy will need to go through the clinical trial process before being widely available | Gene therapy, Gene editing | https://www.youtube.com/watch?v=iWqQiJeP5ac&ab_channel=MayoClinic |
| Codon | a sequence of three letters in the genetic code that corresponds to a speicific amino acid | During translation, the letters in the genetic code are read in triplets. 4H-causing variants often change a codon. | Amino acid, Translation, Variant, Missense | https://www.genome.gov/genetics-glossary/Codon |
| Compound heterozygous | having pathogenic variants in both copies of a specific gene, but these pathogenic variants are different | 4H patients have biallelic pathogenic variants and these can be compound heterozygous or homozygous | Biallelic, Homozygous, Heterozygous, Autosomal receissive, Genotype | https://www.mdpi.com/genes/genes-09-00585/article_deploy/html/images/genes-09-00585-g001.png |
| Corpus Callosum | a white matter structure that connects the right and left sides of the brain so they can communicate with each other | Some individuals with 4H may have a thin corpus callosum seen on MRI | MRI, White matter | https://www.youtube.com/watch?v=xMvVAfZcU1s&ab_channel=NeuroscientificallyChallenged |
| Deciduous teeth | baby teeth or primary teeth that typically start to come in 6 months after birth | The deciduous teeth of 4H patients may erupt in an abnormal order | Hypodontia, Oligodontia, Dentition, Natal teeth | https://www.mouthhealthy.org/en/az-topics/e/eruption-charts |
| Dentition | relating to the development of teeth and their arrangement in the mouth | 4H patients may have delayed dentition or tooth eruption | Hypodontia, Oligodontia, Deciduous teeth, Natal teeth | https://www.mouthhealthy.org/en/az-topics/e/eruption-charts |
| Diffuse | spread out over an area | Most 4H patients have diffuse hypomyelination, meaning myelin is underdeveloped all over the brain, not concentrated in one spot | Hypomyelination, Myelination, Myelin | |
| Disease course | how the disease develops over time | Most 4H leukodystrophy patients develop through the first decade of life, have a period of stability, and then decline. 4H leukodystrophy is a progressive condition but the rate at which it progresses varies. | Natural history, Prognosis | |
| DNA | a spiralling ladder-like molecule that carries our genetic information | 4H leukodystophy is a genetic condition, caused by differences in the DNA | Chromosome, Gene | https://www.youtube.com/watch?v=ictAm2wSwtY&ab_channel=GarvanInstituteofMedicalResearch |
| Dysarthria | slurred speech due to weakness in the muscles used for speech (lips, tongue, vocal cords) | Some 4H leukodystrophy patients may be hard to understand due to dysarthria; a speech-language pathologist should be involved to identify need for assistive communication devices | Dysphagia, Sialorrhea | https://www.nhs.uk/conditions/dysarthria/ |
| Dysmetria | a lack of accuracy in voluntary movements, like misjudging the distance when reaching for an object | Many 4H patients have dysmetria along wih intention tremor | Tremor, Ataxia | https://www.youtube.com/watch?v=jnQcKAYNuyk&ab_channel=MatthewHR1 |
| Dysphagia | difficulty swallowing which can lead to coughing and choking | Dysphagia is common in other leukodystrophies and important to consider in 4H leukodystrophy, especially because it can be progressive | Dysarthria, Sialorrhea, Epilepsy | https://youtu.be/BJJ6E6UQPAk?t=1155 |
| Dystonia | involuntary muscle contractions that cause slow repetitive twisting movements and/or abnormal postures | Dystonia is a common 4H leukodystrophy symptom and is mainly addressed with stretching and sensory pressure tricks | Extramyramidal | https://youtu.be/BJJ6E6UQPAk?t=613 |
| Enyzme | a type of protein that helps speed up chemical reactions in the body | RNA polymerase III is the protein, or more specifically, the enzyme, that is impacted in 4H leukodystrophy | Protein, RNA polymerase III | https://www.youtube.com/watch?v=MvM4L-Qe3vI&t=150s&ab_channel=Teacher%27sPet |
| Epliepsy | seizure disorder | Epilepsy is relatively rare in 4H leukodystrophy patients | Dysphagia, Sialorrhea | https://youtu.be/BJJ6E6UQPAk?t=1480 |
| Exon | coding part of the gene that is important for making proteins | Exons are joined together during a process called splicing. Some 4H leukodystrophy variants disrupt this process. | Splicing, Intron, Variant | https://www.youtube.com/watch?v=YtKoTOCJGt4&ab_channel=ATaleofTwoGenes |
| Extrapyramidal | relating to involuntary and automatic control of the body such as posture and balance | 4H patients can develop extrapyramidal features like dystonia | Dystonia, Pyramidal | https://www.physio-pedia.com/Extrapyramidal_and_Pyramidal_Tracts |
| Failure to thrive | a phrase used when someone does not gain weight at the expected rate | Some 4H patients may have failure to thrive because they have difficulty feeding and swallowing food. They may need a gastrostomy tube to get enough nutrients. | Dysarthria, Gastrostomy/G-tube | https://gikids.org/nutrition/failure-to-thrive/ |
| Founder mutation | A pathogenic variant that has high frequency in a specific population because of geographic or cultural isolation | An example of a founder mutation for 4H leukodystrophy is the c.2015G>A pathogenic variant in POLR3A, commonly found in patients with French Canadian ancestry | POLR3A, Mutation, Variant, Pathogenic | https://www.youtube.com/watch?v=W0TM4LQmoZY&ab_channel=AmoebaSisters |
| Functional study | attempts to understand the effect of a pathogenic variant on the function of a gene or the protein it codes for | Functional studies help us understand how pathogenic variants in POLR3 genes impair the function of RNA polymerase III | RNA polymerase III, Gene, Mouse model | https://www.youtube.com/watch?v=NuMQltP7XMs&ab_channel=ClinGenResource |
| Gastrostomy/G-tube | a tube inserted through the belly that brings nutrition directly to the stomach | Some 4H patients may need a G-tube if they have trouble swallowing food | Dysphagia | https://www.chop.edu/treatments/gastrostomy-tubes# |
| Gene | A segment of DNA that provides instructions for the body | So far we know four genes associated with 4H leukodystrophy: POLR3A, POLR3B, POLR1C, POLR3K | DNA, Chromosome, POLR3A, POLR3B, POLR1C, POLR3K | https://www.youtube.com/watch?v=5MQdXjRPHmQ&ab_channel=StatedClearly |
| Gene editing | makes a small and controlled change to the DNA to treat disease by fixing the underlying genetic cause | In the future, gene editing could be used to treat or cure 4H leukodystrophy | Gene therapy, Clinical trial, Mouse model | https://www.youtube.com/watch?v=I5_2c52OPFw&ab_channel=WellcomeTrust |
| Gene therapy | delivers genetic material to treat disease by addressing the underlying genetic cause | In the future, gene therapy could be used to treat or even cure 4H leukodystrophy | Gene editing, Clinical trial, Mouse model | https://patienteducation.asgct.org/gene-therapy-101/gene-therapy-basics |
| Genotype | the genetic makeup or particular set of genes carried by an individual (influences their phenotype) | 4H patients have a homozygous or compound heterozygous genotype, carriers of 4H leukodystrophy are heterozygous, people without any genetic changes related to 4H are considered wildtype | Phenotype, Homozygous, Compound heterozygous, Heterozygous, Wildtype | https://www.genome.gov/genetics-glossary/genotype |
| Genotype-phenotype correlation | the relationship between specific genetic variants and the clinical presentation they produce | Researchers study genotype-phenotype correlations for 4H leukodystrophy to identify any patterns to better predict the disease course based on a patient’s specific variants | Genotype, Phenotype, Disease course | |
| Gray matter | areas of the brain that are mostly made up of neuron cell bodies and unmyelinated axons | 4H leukodystrophy is a white matter disease, so the gray matter is less affected | White matter, Neuron, Axon, Myelin | https://www.technologynetworks.com/neuroscience/articles/gray-matter-vs-white-matter-322973 |
| Growth hormone deficiency | insufficient production of growth hormone in the body that can result in short stature | Some 4H patients have growth hormone deficiency in addition to the more common endocrine difference, hypogonadotropic hypogonadism | Hypogonadotropic hypogonadism, Short stature | https://www.hormone.org/diseases-and-conditions/growth-hormone-deficiency |
| Heterogenous | diverse or varied | Leukodystrophies are a heterogenous group of conditions | Leukodystrophy | https://www.thoughtco.com/heterogeneous-definition-and-example-606355 |
| Heterozygous | having a pathogenic variant in only one copy of a specific gene | Carriers of 4H leukodystrophy are heterozygous | Carrier, Homozygous, Compound heterozygous, Autosomal recessive, Genotype | https://www.mdpi.com/genes/genes-09-00585/article_deploy/html/images/genes-09-00585-g001.png |
| Homozygous | having identical pathogenic variants in both copies of a specific gene | 4H patients have biallelic pathogenic variants and these can be homozygous or compound heterozygous | Biallelic, Compound heterozygous, Heterozygous, Autosomal recessive, Genotype | https://www.mdpi.com/genes/genes-09-00585/article_deploy/html/images/genes-09-00585-g001.png |
| Hypodontia | missing teeth | Represents an H in 4H leukodystrophy because it is a common clinical feature, including many other teeth differences | Oligodontia, Deciduous teeth, Natal teeth, Dentition | http://www.hypodontia.com/p/what-is-hypodontia.html |
| Hypogonadotropic hypogonadism | delayed, arrested, or absent puberty due to low levels of sex hormones | Represents an H in 4H leukodystrophy because it is a common clinical feature | Primary amenorrhea, Hypodontia, Hypomyelination | https://medlineplus.gov/ency/article/000390.htm |
| Hypomyelinating | describes conditions in which a low level of myelination during development leads to a permanent deficiency in myelin | 4H falls within the hypomyelinating classification of leukodystrophy | Myelin, Myelination, Hypomyelination, Leukodystrophy | |
| Hypomyelination | a low level of myelination during development which leads to a permanent myelin deficiency | Represents an H in 4H leukodystrophy because it is a key feature | Myelination, Myelin, Hypodontia, Hypogonadotropic hypogonadism | |
| Hypothesis | a proposed explanation | Researchers have made hypotheses about the pathophysiology of 4H leukodystrophy, since we still don’t fully understand how these genetic changes lead to the disease | Pathophysiology | |
| Hypothyroidism | the thyroid gland doesn’t produce enough thyroid hormones | Hypothyroidism is a common 4H leukodystrophy symptom; individuals should follow with an endocrinologist | Hypogonadotropic hypogonadism, Growth hormone deficiency | https://www.thyroid.org/hypothyroidism/ |
| Induced pluripotent stem cells (iPSC) | specialized cells that have been taken from the body and reprogrammed so they can differentiate into any type of cell | Researchers are currently investigating how induced pluripotent stem cells could be used to treat 4H leukodystrophy | Gene therapy, Clinical trial, Mouse model | https://vimeo.com/77546203 |
| Intrafamilial variability | when family members with the same genetic condition have different signs and symptoms | 4H has intrafamilial variability, meaning we can’t assume that affected siblings will have the same experience | Autosomal recessive | |
| Intron | non-coding part of the gene that mostly acts like a space-filler between exons | Introns are removed during a process called splicing. Some 4H leukodystrophy variants disrupt this process. | Splicing, Exon, Variant | https://www.youtube.com/watch?v=YtKoTOCJGt4&ab_channel=ATaleofTwoGenes |
| Leukodystrophy | the deteroiration of white matter in the brain which can cause developmental regression | 4H leukodystrophy is one of a handful of leukodystrophy conditions | White matter, Regression | https://www.youtube.com/watch?v=eQjc951qrCw&ab_channel=TheChildren%27sHospitalofPhiladelphia |
| Magnetic Resonance Imaging (MRI) | a scan that produces detailed images of the organs and tissues in the body | MRI is a key diagnostic tool because it can detect hypomyelinating patterns in the brain tissue that are characteristic of 4H leukodystrophy | Hypomyelinating, Hypomyelination, White matter | https://www.chop.edu/treatments/magnetic-resonance-imaging-mri |
| Missense | a type of variant that leads to the substitution of an amino acid in the resulting protein | Most variants causing 4H leukodystrophy are missense variants | Variant, Nonsense, Amino acid, Protein | https://medlineplus.gov/genetics/understanding/mutationsanddisorders/possiblemutations/ |
| Molecular | often refers to the level of the cell or DNA | Molecular information for 4H leukodystrophy patients involves their genetic variants | DNA, Variant, Gene | |
| Mouse model | animals used in the laboratory to mimic and study human disease | Mouse models help us learn about the mechanisms behind 4H leukodystrophy and test potential drugs before they enter clinical trials | Clinical trial | https://www.youtube.com/watch?v=hc0GFLX7AvE&ab_channel=TheJacksonLaboratory |
| Mutation | a harmful change, or typo, in the genetic code; also known as ‘pathogenic variant’ | Mutations in POLR3A, POLR3B, POLR1C, and POLR3K genes cause 4H leukodystrophy | Variant, Pathogenic, DNA, Gene, Chromosome | https://www.genome.gov/genetics-glossary/Mutation |
| Myelin | a fatty, protective coating that wraps around the axons of nerve cells (like the insulation layer around an electrical wire) to allow quick communication of electrical signals through the cell. | Individuals with 4H don’t make enough myelin during development | Myelination, Axon, Neuron, White matter | https://www.youtube.com/watch?v=5V7RZwDpmXE&ab_channel=NeuroscientificallyChallenged |
| Myelination | the formation of myelin sheaths around neuron axons primarily in the first two years of life | Individuals with 4H have a low level of myelination during development, which is known as hypomyelination | Hypomyelination, Myelin, Neuron, Axon | https://www.youtube.com/watch?v=zLan1UrSCxk&ab_channel=EricaHolt |
| Myopia | nearsightedness (faraway objects are blurry) | Almost all 4H leukodystrophy patients have myopia. It is usually severe and progressive. Individuals will need glasses and should follow with an ophthalmologist. | Ocular, Optic atrophy, Nystagmus | https://youtu.be/ldfJGTC0ZQ0?t=51 |
| Natal teeth | teeth that are present when a baby is born | Natal teeth are a less common dental abnormality in 4H | Hypodontia, Oligodontia, Dentition, Deciduous teeth | https://www.stanfordchildrens.org/en/topic/default?id=natal-teeth-90-P01862 |
| Natural history | the usual course of a disease, especially without treatment | There is not yet a 4H leukodystrophy natural history study, but this will be valuable to help families understand what to expect and to compare the effectiveness of future treatments | Disease course, Prognosis | |
| Neurology | branch of medicine that specializes in disorders of the nervous system | Individuals with 4H leukodystrophy will need to see a neurologist regularly | Radiology, Neuropathology | https://www.youtube.com/watch?v=YkIT4HJ46o8&ab_channel=AANChannel |
| Neuron (Nerve cell) | sends and receives information throughout the brain and body using electrical and chemical signals | Because individuals with 4H don’t make enough myelin during development, neurons can’t send messages as quickly through their axons | Axon, Myelin, Oligodendrocyte | https://www.youtube.com/watch?v=rsMjUvMXxpE&ab_channel=Teacher%27sPet |
| Neuropathology | branch of medicine that studies the causes and effects of nervous system disease by examining samples of brain tissue | Some 4H leukodystrophy research involves neuropathology study to better understand the disease | Neurology, Pathophysiology | https://www.vumc.org/pmi/division-neuropathology |
| Nonsense | A type of variant that causes a premature stop, resulting in a shorter, incomplete protein that is usually nonfunctional | Nonsense variants are rare causes of 4H leukodystrophy and never found to be homozygous, or in both copies of the gene | Variant, Missense, Homozygous, Protein | https://medlineplus.gov/genetics/understanding/mutationsanddisorders/possiblemutations/ |
| Nonsense-mediated decay | a quality-control mechanism in the body that recognizes and eliminates messenger RNAs that have a premature stop to avoid producing truncated protein | In 4H patients with rare nonsense variants, nonsense-mediated decay occurs | Nonsense, Variant | https://en.wikipedia.org/wiki/Nonsense-mediated_decay |
| Nystagmus | involuntary movement of the eyes, rapidly and repetitively – side-to-side, up and down, or in a circle | Nystagmus is a common 4H leukodystrophy symptom | Ocular, Myopia, Optic atrophy | https://www.youtube.com/watch?v=VolVn8SqYoY&ab_channel=Rehabmart |
| Ocular | related to the eyes or vision | Almost all 4H patients have myopia. Other, less common, ocular symptoms include optic atrophy and cataracts | Myopia, Optic atrophy, Nystagmus | |
| Oligodendrocyte | cells in the brain that make myelin | Differences in oligodendrocytes may be responsible for the hypomyelination in 4H leukodystrophy | Myelin, Hypomyelination, Axon, Neuron | https://scienceofpd.files.wordpress.com/2020/06/oligodendrocytemyelin.png |
| Oligodontia | the absence of six or more teeth | Oligodontia is a common 4H leukodystrophy symptom, as are many other teeth differences | Hypodontia, Deciduous teeth, Natal teeth, Dentition | http://www.hypodontia.com/p/what-is-hypodontia.html |
| Onset | the first appearance of signs or symptoms | The age of onset for most 4H leukodystrophy patients is before 6 years, though later and even adult onset has been reported | Disease course, Prognosis, Natural history | |
| Optic atrophy | loss of nerve fibers that send images from the retina of the eye to the brain resulting in vision issues | Optic atrophy is a less common symptom of 4H leukodystrophy | Myopia, Ocular, Nystagmus | https://www.allaboutvision.com/resources/anatomy.htm |
| Pathogenic | disease-causing or harmful | Pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K genes cause 4H leukodystrophy | Mutation, Variant | |
| Pathophysiology | how dieseases affect the systems of the body and cause changes that lead to health consequences | Researchers are still trying to fully understand the pathophysiology of 4H leukodystrophy | Neuropathology, Neurology | https://www.youtube.com/watch?v=C3DakmykRiI&ab_channel=bionerdery |
| Phenotype | an individual’s observable characteristics | In addition to height, eye color, and hair color, a 4H patient’s phenotype includes their clinical features like teeth differences, delayed puberty, and nearsightedness for example | Genotype, Genotype-phenotype correlation | https://www.genome.gov/genetics-glossary/Phenotype |
| POL3RA | when italisized, it refers to the gene that codes for the largest subunit of RNA polymerase III; when not italisized, it refers to the protein subunit itself | Pathogenic variants in both copies of the POLR3A gene cause 4H leukodystrophy | Gene, POLR3B, POLR1C, POLR3K, Variant, Pathogenic, RNA Polymerase III | |
| POL3RB | when italisized, it referes to a gene that codes for a subunit of RNA polymerase III; when not italisized, it refers to the protein subunit itself | Pathogenic variants in both copies of the POLR3B gene cause 4H leukodystrophy | Gene, POLR3A, POLR1C, POLR3K, Variant, Pathogenic, RNA Polymerase III | |
| POLR1C | when italisized, it refers to a gene that codes for a shared subunit of RNA polymerase I and III; when not italisized, it refers to the protein subunit itself | Pathogenic variants in both copies of the POLR1C gene cause 4H leukodystrophy | Gene, POLR3A, POLR3B, POLR3K, Variant, Pathogenic, RNA Polymerase III | |
| POLR3K | when italisized, it refers to a gene that codes for a subunit of RNA polymerase III; when not italisized, it refers to the protein subunit itself | Pathogenic variants in both copies of the POLR3K gene cause 4H leukodystrophy | Gene, POLR3A, POLR3B, POLR1C, Variant, Pathogenic, RNA Polymerase III | |
| Polymerase | an enzyme in the body that assembles DNA or RNA molecules by copying a DNA template | The function of RNA polymerase III is impacted in 4H leukodystrophy | Enzyme, RNA Polymerase III, Protein | https://www.technologynetworks.com/genomics/articles/rna-polymerase-function-and-definition-346823 |
| Primary amenorrhea | the absence of menstruation or periods after age 15 | Primary amenorrhea is a sign of delayed puberty in female 4H patients | Hypogonadotropic hypogonadism | https://www.mayoclinic.org/diseases-conditions/amenorrhea/symptoms-causes/syc-20369299 |
| Prognosis | a prediction of how a patient’s disease will progress and the likely outcome | 4H leukodystrophy is considered life-limiting but the prognosis can be difficult to predict because each individual’s experience is unique. | Disease course, Natural history | |
| Protein | a complex molecule made up of long, folded chain(s) of amino acids that has an important job in the body | RNA polymerase III is the protein, or more specifically, the enzyme, that is impacted in 4H leukodystrophy | Amino acid, Enzyme, RNA polymerase III, Translation | https://www.youtube.com/watch?v=JGZj6DsUZhE&ab_channel=FuseSchool-GlobalEducation |
| Pyramidal | relating to voluntary control of the body | 4H patients often develop mild pyramidal features like spasticity | Spasticity, Extrapyramidal | https://www.physio-pedia.com/Extrapyramidal_and_Pyramidal_Tracts |
| Radiology | branch of medicine that uses imaging technology to diagnose disease | Radiologists read and interpret MRI scans, which are often important for diagnosing 4H leukodystrophy | Magnetic Resonance Imaging (MRI), Neurology | https://www.youtube.com/watch?v=k0rWScAt32w&ab_channel=NemoursKidsHealth |
| Regression | loss of previously acquired skills | Some 4H patients develop typically at first and then regress, losing skills they had been using regularly | Prognosis, Disease course, Natural history | |
| RNA | molecules copied from DNA templates that have various tasks in the cell; one type carries the information to make a protein (messenger RNA) | Messenger RNA is important in the process to make the subunits of RNA polymerase III from POLR3 genes. The job of RNA polymerase III is to make many small RNAs that help regulate the cell. | DNA, Translation, RNA Polymerase III, Gene | https://www.news-medical.net/life-sciences/-Types-of-RNA-mRNA-rRNA-and-tRNA.aspx |
| RNA Polymerase III | an enzyme that assembles small RNAs that don’t code for proteins but regulate important processes in the cell | The function of RNA polymerase III is impacted in 4H leukodystrophy | Polymerase, Protein, Enzyme | https://www.youtube.com/watch?v=v_Ou1mIqvhk&ab_channel=YayaFoundationfor4HLeukodystrophy |
| Short stature | describing height that is considerably below the average height of their peers (specifically, two standard deviations below) | About half of 4H leukodystrophy patients have short stature | Hypogonadotropic hypogonadism, Growth hormone deficiency | https://www.yalemedicine.org/conditions/short-stature-child |
| Sialorrhea | drooling | Sialorrhea after 2 years is common in other leukodystrophies and important to consider in 4H leukodystrophy | Dysarthria, Dysphagia, Epilepsy | https://youtu.be/BJJ6E6UQPAk?t=1366 |
| Spasticity | stiffness or tightness due to increased muscle tone | Spasticity is a common 4H leukodystrophy symptom and is mainly addressed with lots of stretching | Pyramidal | https://youtu.be/BJJ6E6UQPAk?t=425 |
| Splicing | after transcription, the noncoding parts (introns) of the gene are removed from the messenger RNA and the remaining pieces (exons) are joined together | Some pathogenic variants that cause 4H leukodystrophy are splice site variants, which interrupt the splicing process | Intron, Exon, Transcription Alternative splicing | https://www.youtube.com/watch?v=aVgwr0QpYNE&ab_channel=DNALearningCenter |
| Thalamus | a gray matter structure in the brain that relays signals to the cerebral cortex | In addition to hypomyelination and cerebellar atrophy, sometimes a signal in the thalamus is seen on MRI of 4H patients | Gray matter, Hypomyelination, Cerebellar atrophy | https://www.youtube.com/watch?v=IF8_82e9RmQ&ab_channel=NeuroscientificallyChallenged |
| Transcription | the process by which the genetic code in DNA is copied into a strand of RNA. This is carried out by RNA polymerases. | Normally, 4H leukodystrophy genes are transcribed into messenger RNAs that are then translated into proteins that make up RNA polymerase III. Pathogenic variants in these genes can disrupt these processes, preventing RNA polymerase III from working like it should. RNA polymerase III’s job in the body happens to be transcription. | RNA, RNA polymerase III, Translation, Gene | https://www.youtube.com/watch?v=gG7uCskUOrA&ab_channel=yourgenome |
| Translation | the process by which a protein is built from the genetic code contained in a strand of messenger RNA | Normally, 4H leukodystrophy genes are transcribed into messenger RNAs that are then translated into proteins that make up RNA polymerase III. Pathogenic variants in these genes can disrupt these processes, preventing RNA polymerase III from working like it should. | RNA, RNA polymerase III, Transcription, Gene, Protein | https://www.youtube.com/watch?v=gG7uCskUOrA&ab_channel=yourgenome |
| Tremor | involuntary shaking movement | Tremor is seen in some 4H patients and should be assessed by a a neurologist | Ataxia, Dysmetria | https://medlineplus.gov/tremor.html |
| Variant | a change or typo in the genetic code; a ‘pathogenic variant’ is a newer term for ‘mutation’ | Pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K genes cause 4H leukodystrophy | Mutation, Pathogenic, Gene, DNA, Chromosome | https://www.youtube.com/watch?v=uLgLws_flZk&ab_channel=DenaDNA |
| White matter | areas of the brain that are mostly made up of myelinated axons | 4H leukodystrophy is a white matter disease because there isn’t enough myelin made in the brain | Myelin, Myelination, Hypomyelination, Axon, Corpus callosum, Gray Matter | https://www.youtube.com/watch?v=WHyHC7vLKS0&ab_channel=EmilyWood |
| Whole exome sequencing | a genetic test that reads through all the genes in the body looking for pathogenic variants that might explain a person’s symptoms | If a patient’s symptoms aren’t clearly pointing to a particular condition, whole exome sequencing might be ordered to try to find a genetic explanation. Some 4H patients are diagnosed this way. If 4H leukodystrophy is already suspected, a more specific test looking only at POLR3A, POLR3B, POLR1C, and POLR3K is usually recommended. | Gene, POLR3A, POLR3B, POLR1C, POLR3K | https://www.youtube.com/watch?v=Ie_0trPLM-I&ab_channel=Children%27sNationalHospital |
| Wild-type | refers to the typical, or most common, state | Wild-type can refer to 4H leukodystrophy genes that do not have pathogenic variants or the clinical presentation of a person who does not have 4H leukodystrophy | Gene, Genotype, Phenotype | https://youtu.be/jxNdX_FZnYI?t=32 |
