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      <image:title>Mission - CHILDREN AND FAMILIES</image:title>
      <image:caption>Most PMD children face severe motor impairment along with a number of related physical and intellectual development issues. This creates a varied set of challenges for both the child and the family. Specifically, quality of life becomes a greater concern as the children grow. Parents need help with providing for basic needs. Specialized equipment, such as wheelchairs, walkers, etc., is expensive and often not covered under the families’ health care plans as is sometimes the case with therapies and treatment. From an intellectual standpoint, the severe motor impairment often creates a communication barrier that is more often than not, the greatest hurdle towards further development. Providing access to available technologies can go a long way in enabling these children to get more in touch with the world around them as well as provide them with the opportunity for further development.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1557404765080-JR7FE3W9IDRGSRH8NZIA/IMG_0421.jpg</image:loc>
      <image:title>Mission - THE GENERAL PUBLIC</image:title>
      <image:caption>Although the clinical basis of the disease was described more than 100 years ago, widespread awareness of PMD among the general public is still a significant issue. With symptoms similar to severe Cerebral Palsy, PMD is still misdiagnosed to a large extent. Further, as screening tests have been developed to identify the mutation in suspected carrier mothers, the implications are that increased awareness and medical counseling can go a long way towards reducing the occurrences of the disease.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1557405091599-T7M4IST2Q6E4XDK0NQVY/IMG-0809.JPG</image:loc>
      <image:title>Mission - RESEARCHERS AND CLINICIANS</image:title>
      <image:caption>As PMD is a rare disease, with only thousands of known cases in the world; researchers are faced with a limited pool of data with which to work. This condition directly limits their ability to attract needed funds, as access to clinical data is usually a prerequisite to available grant money. This also increases the need for greater collaboration and coordination between researchers in order to be successful in the shortest amount of time possible. The impetus for forming the foundation was partly inspired by the state of the current research for leukodystrophies and genetic disorders in general. There are many exciting things that are currently happening. Much of what we know about PMD and other leukodystrophies is starting to come together. Currently, researchers working on all types of leukodystrophies are now at the point where several potential means to re-myelinating the central nervous system (CNS) have been identified. At this point, an increased PMD focus is very timely and extremely beneficial to the overall effort to re-myelinate the CNS for two reasons. First, researchers have been successful in working with PMD animal models for myelin research for many years. With these successes, an increased focus on PMD presents the opportunity for direct scale-up to human models. Unlike many other diseases, PMD animal models very closely resemble human models. This is because the PLP gene (where PMD mutations occur) is nearly identical in all animals, including humans. Second, from the standpoint of the myelin researcher, PMD provides an extremely attractive human model to work with. This is because PMD patients typically reach a developmental plateau where their condition remains relatively stable, unlike individuals affected with other leukodystrophies. PMD is not a progressive, demyelinating disease. Human PMD studies can provide researchers with a longer timeframe to study specific patients. PMD research can potentially shorten the timeline towards a cure for all diseases of myelin, including Multiple Sclerosis. At this juncture, it seems possible that, by fostering communication and collaboration between researchers, improving their access to data, and providing direction to their efforts, we now have the opportunity to accelerate the pace towards our ultimate goal of finding a cure for PMD and other leukodystrophies.</image:caption>
    </image:image>
  </url>
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    <loc>https://www.pmdfoundation.org/newsletters</loc>
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    <lastmod>2019-04-05</lastmod>
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      <image:title>Newletter - Fall 2017</image:title>
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    <loc>https://www.pmdfoundation.org/newsletters/ycrzyfz8kb92ywed3bnyen77c5kx56</loc>
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      <image:title>Newletter - Summer 2017</image:title>
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      <image:title>Newletter - Holiday 2016</image:title>
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      <image:title>Newletter - Fall 2016</image:title>
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      <image:title>Newletter - Summer 2016</image:title>
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      <image:title>Newletter - Spring 2016</image:title>
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    <lastmod>2019-06-06</lastmod>
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      <image:title>Doctors &amp; Researchers - Dr. Paul Tesar, DPhil</image:title>
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      <image:title>Doctors &amp; Researchers - Dr. Florian S. Eichler, MD</image:title>
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      <image:title>Doctors &amp; Researchers - Dr. Geneviève Bernard, MD, MSc, FRCPc</image:title>
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      <image:title>Doctors &amp; Researchers - Dr. Grace Hobson, Ph.D. - Make it stand out</image:title>
      <image:caption>Whatever it is, the way you tell your story online can make all the difference.</image:caption>
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      <image:title>What is PMLD?</image:title>
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      <image:title>What is PMLD? - Make it stand out</image:title>
      <image:caption>Whatever it is, the way you tell your story online can make all the difference.</image:caption>
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    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/9436d813-e5b7-4e3d-817d-039a79a17033/PMLDLogo.png</image:loc>
      <image:title>What is PMLD? - Make it stand out</image:title>
      <image:caption>Whatever it is, the way you tell your story online can make all the difference.</image:caption>
    </image:image>
  </url>
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      <image:title>Researchers - Some of the scientists and organizations working on this</image:title>
    </image:image>
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      <image:title>Stem Cells, Inc.</image:title>
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    <lastmod>2025-03-25</lastmod>
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      <image:title>Family Stories</image:title>
      <image:caption>Camden Holmes was diagnosed with PMD at 13-months of age.</image:caption>
    </image:image>
  </url>
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    <loc>https://www.pmdfoundation.org/affected-family-registration</loc>
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  <url>
    <loc>https://www.pmdfoundation.org/what-is-pmd-about</loc>
    <changefreq>daily</changefreq>
    <priority>0.75</priority>
    <lastmod>2024-01-25</lastmod>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1553689962595-Y3RHKWVHZP19MIT8IFO9/pmdf.jpg</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>PMD Foundation board member, Carlos Labrada with his wife, Yezabel and their son Leo, who was diagnosed with PMD at 6 months of age.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562810239298-1PDFTWTM4RKFMW5IGCH7/Sec1+Fig1.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 1. Myelin is produced by cells in the brain called oligodendrocytes that myelinate the axons, which are projections of nerve cells. The cell membrane on the outside of an oligodendrocyte wraps around the axons of several nerve cells. Cell membranes of other oligodendrocytes also wrap the axon until there are sheaths of myelin covering the axons of each nerve cell. The myelin sheaths provides insulation for axons so that nerve impulses can be transmitted rapidly from neuron to neuron without leaking out. This is similar to how we use insulation on electric cords.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562811648647-TE8U41NU2WOUPZWOHUUV/Sec1+Fig2.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 2. There is a wide spectrum of disease severities in PMD/SPG2. Disease severity ranges from the most severe connatal (or congenital) form that is present at birth in which patients never walk or talk to the least severe or spastic paraplegia 2 (SPG2) form in which patients develop the ability to walk and talk, but they decline usually beginning in the teen years.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562811302302-UNM0Y354KRX8Z1MWC8K6/Sec2+Fig1.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 1. A cell showing nucleus with chromosomes. The chromosomes are made of the DNA double helix all wound up and held together by proteins (shown in yellow). Between the two strands of the double helix are the bases (or letters A, T, G, and C) that are responsible for the genetic code. The bases on one side of the helix are bonded to the complementary bases on the other side of the helix. A always pairs with T, and G always pairs with C. A gene is a stretch of DNA that codes for a protein.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562810603507-3EJYKOJ7HGJOZ7M55XRJ/Sec2+Fig2.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 2. The karyotype of a normal person. The karyotype with chromosomes grouped by size shows that humans normally have 23 pairs of chromosomes. One chromosome of each pair came from the person’s mother and the other from his/her father. This is the karyotype of a male as there is an X and a Y.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562810669022-QGGAXOCLMMEYQJMRBJGC/Sec2+Fig3.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 3. Proteins, which are coded by DNA, are made of a linear string of amino acids. In this diagram, the amino acids are represented by circles. There are 20 amino acids that can be used in various combinations to make proteins. In an expanded region of the protein, the amino acids phenylalanine, leucine, serine, and cysteine are shown. The three-letter standard abbreviations for these amino acids is shown in circles. There are also a one-letter standard abbreviations that are sometimes used. In the large circle, you can see the chemical elements that are the same for every amino acid, plus the R group that differs for each of the 20 amino acids and gives them their different properties.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562810705575-9Y5TF4QCCH3MAXHZT1J7/Sec2+Fig4.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 4. How the genetic code works. There is a flow of information from DNA to RNA to protein. The double helix of the DNA shown in this diagram is stretched out flat. Between the two strands of the double helix are the bases that make the 3-letter words (codons) of the genetic code. There are four bases: adenine (A), thymidine (T), cytosine (C), and guanine (G). The bases on the top strand are complementary to the bases on the bottom strand. A on one strand always pairs with T on the other, and C always pairs with G. The bases on one strand are weakly bonded to the bases on the other strand (shown by dashed lines), so that the strands of DNA can be zipped apart and the cellular machine that “reads” the DNA code and makes the RNA strand can get to the strand that gets copied. The RNA strand will have the same code as the DNA, except that it uses the base called uracil (U) instead of T. Another cellular machine then “reads” the RNA three-letter words one codon at the time and adds the specified amino acids one at the time to the growing protein. The dots mean “and so on,” as the code goes on to make a protein with many amino acids, while only 4 are shown here.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562811707162-M7Q1TMSA4PI0PZ759TZT/Sec2+Fig5.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 5. Splicing of the RNA. Splicing must occur so that only the expressed parts of the RNA (those that code for the protein) remain in the RNA. The introns (shown in blue) are spliced out and the exons (the parts that codes for the protein, shown in red) will remain.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812170835-MBPPD8KWBWYBO1Z64Z26/Sec3+Fig1.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 1. The PLP1 gene is on the long arm (the p-arm) of the X chromosome. Giemsa banding (or G-banding) is a technique used to make a characteristic banding pattern appear on each of the chromosomes. The PLP1 gene is located in a band on the X chromosome called Xq22.3.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812229698-CRVQQCJ2RTTOVOMAWTY0/Sec3+Fig2.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 2. PLP protein sits in the cell membrane of oligodendrocytes. Like all other proteins, PLP is made of a string of amino acids. Each circle in the diagram with a letter inside represents an amino acid in the string that makes up the PLP protein. The one-letter abbreviations for amino acids are used here. M is for the first amino acid methionine; G is for glycine; L is for leucine; and another L for the next amino acid which is another leucine, etc. There is also a 3-letter abbreviation for each amino acid. There are 20 different amino acids. The dark circles with zig-zag lines represent the lipid bilayer that makes up the cell membrane. The amino acids that run through the lipid bilayer are in the oligodendrocyte cell membrane. Those that are above it are on the outside of the cell membrane, and those that are below it are on the inside of the cell in the cytoplasm, the substance that fills cells.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812275581-A2BVTAJ2ILX8WIMQ1IGH/Sec3+Fig3.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 3. X-linked recessive inheritance. PMD has an X-linked recessive inheritance pattern. It is X-linked because the PLP1 gene is on the X chromosome. It is called recessive because if there is an affected copy of the gene on one chromosome and an unaffected copy on the X chromosome that is paired with it in a female, the unaffected copy is able to compensate for the affected copy and the female does not have PMD. This diagram of X-linked recessive inheritance shows that an unaffected father and a mother who is a carrier (has an unaffected copy of the PLP1 gene on one of her X chromosomes and an affected copy on the other) will have (shown left to right) the following probabilities for their offspring: ¼ (25%) unaffected son, ¼ (25%) unaffected daughter (not a carrier), ¼ (25%) carrier daughter, and ¼ (25%) affected son.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812781235-1FZV0LM3BRDGT6YHJYGP/Sec4+Fig1.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 1. The most common variant causing PMD is duplication. A duplication occurs when a part of the chromosome is doubled. Duplications can affect many genes in addition to PLP1.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812870878-6N64MC7FF0SQZ2UYT3JR/Sec4+Fig2.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 2. Rarely, complete deletion of a chromosomal region causes PMD.</image:caption>
    </image:image>
    <image:image>
      <image:loc>https://images.squarespace-cdn.com/content/v1/5c65847bab1a625acb418894/1562812916594-2SCFOG7OKQPPFJ2S2HC2/Sec4+Fig3.png</image:loc>
      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 3. Types of variants. A. A missense variant results in an amino acid change. B. A nonsense variant results in a stop codon and termination of the growing chain of amino acids. C. A deletion or duplication variant of one or several bases (in this case, a deletion of two bases) shifts the reading frame, so the wrong amino acids get added to the protein. What was originally the word GTA coding for Val is shifted to the word GCC, which also codes for Val, but then the next word is CTA coding for Leu rather than CCC coding for Pro. The remaining codons are frame shifted until a stop codon is reached by chance and then the growth of the amino acid chain is terminated. Addition of one or a few bases can have the same result as deletion.</image:caption>
    </image:image>
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      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 4. Splicing variants. Splicing variants can cause exons to be skipped or introns to be retained in the RNA that gets translated to protein. It can also cause only parts of the protein to be made.</image:caption>
    </image:image>
    <image:image>
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      <image:title>What is PMD - About</image:title>
      <image:caption>Figure 5. The wide clinical spectrum of disease severity (see “What is PMD?” section) is reflected in the variety of types of variants that cause PMD/SPG2.</image:caption>
    </image:image>
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