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"slug": "amid-intense-isolation-stirrings-of-hope-for-families-with-rarest-genetic-mutations",
"title": "Stirrings of Hope for Families Isolated by Rarest of Genetic Conditions",
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"content": "\u003cp>Shortly after \u003ca href=\"http://milosjourney.com/\" target=\"_blank\" rel=\"noopener\">Milo Lorentzen\u003c/a> was born, nurses whisked him away to the neonatal intensive care unit for low blood sugar and jaundice. An exam then found a cluster of irregularities, including a cleft palate and a hole in his heart.\u003c/p>\n\u003cp>The staff called in a geneticist, who issued a misdiagnosis—the first frustrating episode in what would become years of testing, as Karen Park and Peter Lorentzen searched for a way to help their son.\u003c/p>\n\u003caside class=\"pullquote alignright\">‘You’re the ‘other-other,’ and not just the ‘other.'”\u003ccite>Karen Park, Milo’s mother\u003c/cite>\u003c/aside>\n\u003cp>Five years later, Park and Lorentzen know Milo’s significant developmental delays likely stem from a mutation in a gene called KDM1A. He didn’t inherit that mutation from his parents; it’s new in Milo. And because a mutation in that gene is so rare, little is known about it. There is no treatment.\u003c/p>\n\u003cp>If KDM1A is indeed the culprit, Milo has what’s known as a \u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK132145/\" target=\"_blank\" rel=\"noopener\">Mendelian disorder\u003c/a>—a rare condition caused by a genetic mutation, typically in a single gene. There are some 7,000-8,000 known Mendelian conditions, but researchers have found the genetic cause for only half. The rest are identified as Mendelian because they are transmitted from parents to children in ways suggesting they are caused by single genes.\u003c/p>\n\u003cp>In some cases—and researchers say Milo’s appears to be one of them—a new mutation reveals a new condition, previously unidentified.\u003c/p>\n\u003cp>[ad fullwidth]\u003c/p>\n\u003cp>Families with an unidentified genetic illness are lost in an information desert, isolated by protocols that protect research until published, and by health privacy laws that prevent, for example, a genetics lab from connecting two families with the same mutation.\u003c/p>\n\u003cp>The journey of Milo Lorentzen reveals what \u003ca href=\"https://www.bcm.edu/people/view/christian-schaaf-m-d-ph-d/b251d11c-ffed-11e2-be68-080027880ca6\" target=\"_blank\" rel=\"noopener\">Dr. Christian Schaaf\u003c/a>, an assistant professor at \u003ca href=\"https://www.bcm.edu/\" target=\"_blank\" rel=\"noopener\">Baylor College of Medicine\u003c/a>, says are two major inadequacies in genetic medicine—the absence of support for families with undiagnosed illnesses, and the lack of a clearinghouse where families and researchers can find one another.\u003c/p>\n\u003cp>[contextly_sidebar id=”y6fCjzsdBLr9bsR5jKAH3kyZ56BhiTeO”]“We all worry about the correct diagnosis, and therapy, and management of the disease,” Schaaf says, “but we don’t think enough about the isolation these families feel, about the stress and anxiety that comes with these disorders.”\u003c/p>\n\u003cp>Recently, however, new and cheaper techniques in genetic testing and efforts to connect families to each other and to researchers offer promise of a future less desolate.\u003c/p>\n\u003cp>“There are lots of researchers who might be interested in families with genetic conditions if they knew they existed,” says \u003ca href=\"http://depts.washington.edu/bamshad/\" target=\"_blank\" rel=\"noopener\">Dr. Michael Bamshad\u003c/a>, principle investigator of the \u003ca href=\"http://uwcmg.org/#/\" target=\"_blank\" rel=\"noopener\">University of Washington Center for Mendelian Genomics\u003c/a>.\u003c/p>\n\u003cp>Bamshad is cofounder of \u003ca href=\"https://www.mygene2.org/MyGene2/\">MyGene2\u003c/a>, a website where families, researchers, and clinicians can connect and share information at no cost. The site is a \u003ca href=\"https://www.openscienceprize.org/res/p/finalists/\">finalist\u003c/a> in a National Institutes of Health competition to make scientific information broadly available.\u003c/p>\n\u003cp>\u003cstrong>‘You’re the Other-Other’\u003c/strong>\u003c/p>\n\u003cp>When your child has an undiagnosed genetic disorder, one of life’s hallmarks is a frustrating series of tests yielding no answers.\u003c/p>\n\u003cp>“The first several years of his life was test after test,” says Karen Park, Milo’s mother. “X-rays, MRIs, blood tests, skin biopsies.”\u003c/p>\n\u003cfigure id=\"attachment_174418\" class=\"wp-caption aligncenter\" style=\"max-width: 2048px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg\" alt=\"Milo Lorentzen is learning to read and speak using an alternative language method that incorporates symbols and pictures. He now reads at or above grade level. “He was starting to have behavioral issues until we gave him this method,” says his mother, Karen Park. “Now Milo has a voice.” \" width=\"2048\" height=\"1536\" class=\"size-full wp-image-174418\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg 2048w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-400x300.jpg 400w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-800x600.jpg 800w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-768x576.jpg 768w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-1180x885.jpg 1180w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-1920x1440.jpg 1920w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-960x720.jpg 960w\" sizes=\"(max-width: 2048px) 100vw, 2048px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Milo Lorentzen is learning to read and speak using an alternative language method that incorporates symbols and pictures. “He was starting to have behavioral issues until we gave him this method,” says his mother, Karen Park. “Now Milo has a voice.” \u003ccite>(Marissa Miller)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Milo had a range of symptoms: low muscle tone and a body that lacked strength, making him slow to lift his head or push up off his stomach; and delays in mimicking people and expressing himself. To his doctors, these symptoms suggested many possibilities.\u003c/p>\n\u003cp>“It takes forever; it’s very slow,” Park says. “And when things keep coming back negative, you feel like: My child is getting tortured; I’m not getting any insight out of this; I just feel like giving up.”\u003c/p>\n\u003cp>Many rare disorders affect at least enough families to constitute what Park calls a tribe: parent groups, coping tips, research tools, and fundraising walks.\u003c/p>\n\u003cp>But Milo’s parents were on their own.\u003c/p>\n\u003cp>Researchers know of only two other children in the world who have a genetic mutation similar to Milo’s. In fact, KDM1A is known to be resistant to evolutionary change; a mutation is so rare researchers hardly ever see it in any animal species.\u003c/p>\n\u003cp>“You’re the ‘other-other’ and not just the ‘other,’” Park says.\u003c/p>\n\u003cfigure id=\"attachment_174447\" class=\"wp-caption aligncenter\" style=\"max-width: 720px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174447\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg\" alt=\"Tess Bigelow is six years old and funtions at an 18-month-old level. Recently she walked 100 meters in the Special Olympics.\" width=\"720\" height=\"753\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg 720w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-400x418.jpg 400w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-574x600.jpg 574w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-32x32.jpg 32w\" sizes=\"(max-width: 720px) 100vw, 720px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Tess Bigelow is six years old and funtions at an 18-month-old level. Recently she walked 100 meters in the Special Olympics. \u003ccite>(Bo Bigelow)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Bo Bigelow, whose daughter Tess is one of only 10 people in the world known to have a mutation in a gene called USP7, went five years before he knew there was anyone else with a similar mutation.\u003c/p>\n\u003cp>“These days there are ribbons and awareness weeks for so many diseases,” Bigelow says, “but when yours is ultra-rare, you feel completely isolated. You feel like you’re never going to hear another person say, ‘Us too!’ And being connected to other families changes all that.”\u003c/p>\n\u003cp>\u003cstrong>Pinpointing the Problem\u003c/strong>\u003c/p>\n\u003cp>In 2013, Milo’s parents had his genes sequenced with a relatively new technique called exome sequencing, which streamlines the process by looking only at genes that code for proteins, and not all an individual’s DNA. It was then they learned about Milo’s gene mutation.\u003c/p>\n\u003cp>Still, mutations in KD1MA are so rare that just spotting it didn’t give Milo’s parents a diagnosis.\u003c/p>\n\u003cp>Why not?\u003c/p>\n\u003cp>“We don’t know what most of our genes do,” says geneticist Barry Starr.\u003c/p>\n\u003cfigure id=\"attachment_174450\" class=\"wp-caption alignright\" style=\"max-width: 250px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/DNA-1.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174450\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/DNA-1.jpg\" alt=\"Genes issue instructions to make proteins, which run the functions of our cells. Genes make up 1-2 percent of our DNA.\" width=\"250\" height=\"371\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Genes issue instructions to make proteins, which run the functions of our cells. Genes make up 1-2 percent of our DNA. \u003ccite>(National Institutes of Health)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Genes issue instructions to make proteins that run the functions of a cell. But discovering what any single gene mutation does is complicated.\u003c/p>\n\u003cp>You need to know how the mutation affects the proteins, and how the proteins related to the disease. You also want to know whether the mutation has appeared in other family members who have experienced symptoms.\u003c/p>\n\u003cp>“You’re playing all these games like a detective story,” says Starr, “trying to solve a mystery.”\u003c/p>\n\u003cp>One way to get a diagnosis is by looking at previous research.\u003c/p>\n\u003cp>Dr. Michael Bamshad once found a mutation in a gene called MYLPF in a boy who had no muscles in his foot. Bamshad found a mouse study in which researchers had made a deliberate mutation MYLPF, resulting in a complete lack of skeletal muscle in the rodent. That was enough evidence to conclude the MYLPF gene was involved in the boy’s condition.\u003c/p>\n\u003cp>But sometimes there is no published research.\u003c/p>\n\u003cp>Bigelow says geneticists who told him of Tess’ mutation didn’t know what the USP7 gene did.\u003c/p>\n\u003cp>“We know this is the gene, but we don’t know anything more than that,” says Bigelow.\u003c/p>\n\u003cp>\u003cstrong>Easing the Isolation\u003c/strong>\u003c/p>\n\u003cp>Bigelow put out a beacon to other families who might have the same mutation: \u003ca href=\"http://www.portlandrootsmedia.com/tess-genetic-mystery\" target=\"_blank\" rel=\"noopener\">a website\u003c/a> and social media posts. Remarkably, it took \u003ca href=\"http://ww2.kqed.org/futureofyou/2016/05/10/social-media-uncovers-rare-diagnosis-after-years-of-frustration/\" target=\"_blank\" rel=\"noopener\">less than a day\u003c/a> for a response. Researchers are now examining his daughter’s case, and at their request Bigelow has used his website to find two more families with the same mutation.\u003c/p>\n\u003cp>But it’s a lot slower for families and researchers to search through hundreds of websites and Facebook pages for common ground.\u003c/p>\n\u003cp>\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/My-gene2.png\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-174459\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/My-gene2.png\" alt=\"My gene2\" width=\"627\" height=\"264\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/My-gene2.png 627w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/My-gene2-400x168.png 400w\" sizes=\"(max-width: 627px) 100vw, 627px\">\u003c/a>\u003c/p>\n\u003cp>Now Bigelow and Milo Lorentzen’s parents are registered on MyGene2, where roughly 130 families are seeking information on mutations in more than \u003ca href=\"https://www.mygene2.org/MyGene2/genes\" target=\"_blank\" rel=\"noopener\">100 genes\u003c/a>.\u003c/p>\n\u003cp>Bamshad envisions expanding that to tens of thousands of families.\u003c/p>\n\u003cp>“Our major goal is gene discovery and facilitating clinical diagnosis,” he says. “Very quickly, we could identify hundreds of Mendelian conditions and help thousands of families get a diagnosis for rare diseases.”\u003c/p>\n\u003cp>The main stumbling block is money to pay for outreach, Bamshad says. Tens of thousands of exome sequences are siloed at individual labs and clinics around the country. Because of federal privacy laws, the only people who can share those are the families who had them commissioned.\u003c/p>\n\u003cp>“We see lots of families on Facebook who are searching for a diagnosis,” says geneticist \u003ca href=\"https://depts.washington.edu/genediv/directory/jchong\" target=\"_blank\" rel=\"noopener\">Jessica Chong\u003c/a>, MyGene2 cofounder. “It would take time to go search for them and message each one of them to say, ‘We can help you.’”\u003c/p>\n\u003cfigure id=\"attachment_174559\" class=\"wp-caption aligncenter\" style=\"max-width: 718px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174559\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg\" alt=\"Tess Bigelow stomps it out on the track where she competed in the Special Olympics.\" width=\"718\" height=\"590\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg 718w, https://cdn.kqed.org/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230-400x329.jpg 400w\" sizes=\"(max-width: 718px) 100vw, 718px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Tess Bigelow stomps it out on the track where she\u003ca href=\"http://www.portlandrootsmedia.com/strongerpodcast/2016/5/4/68-special-is-an-understatement\" target=\"_blank\" rel=\"noopener\"> prepares to compete \u003c/a>in the Special Olympics. \u003ccite>(Bo Bigelow)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Dr. Christian Schaaf, who’s working with Tess Bigelow’s mutation, says it has typically taken 15-20 years from the time a disease gene has been discovered until the first patients enter clinical trials. He’s hoping new sequencing tools and social outreach can shrink that to seven or eight years.\u003c/p>\n\u003cp>Milo’s parents hope that new research will give them more answers. They found a U.S. lab that’s agreed to grow cell lines from Milo’s and his father’s DNA, and another lab in Europe is looking to run studies using the gene-editing tool CRISPR.\u003c/p>\n\u003cp>If the labs can replicate Milo’s mutation and study its effects, perhaps Karen Park and Peter Lorentzen will learn more about how the mutation leads to his disorder. From there, will some lab be willing to look at developing a treatment? They don’t know.\u003c/p>\n\u003cp>[ad floatright]\u003c/p>\n\u003cp>“It’s all us flying blind and making it up as we go along,” says Park.\u003c/p>\n\n",
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"title": "Stirrings of Hope for Families Isolated by Rarest of Genetic Conditions",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003cp>Shortly after \u003ca href=\"http://milosjourney.com/\" target=\"_blank\" rel=\"noopener\">Milo Lorentzen\u003c/a> was born, nurses whisked him away to the neonatal intensive care unit for low blood sugar and jaundice. An exam then found a cluster of irregularities, including a cleft palate and a hole in his heart.\u003c/p>\n\u003cp>The staff called in a geneticist, who issued a misdiagnosis—the first frustrating episode in what would become years of testing, as Karen Park and Peter Lorentzen searched for a way to help their son.\u003c/p>\n\u003caside class=\"pullquote alignright\">‘You’re the ‘other-other,’ and not just the ‘other.'”\u003ccite>Karen Park, Milo’s mother\u003c/cite>\u003c/aside>\n\u003cp>Five years later, Park and Lorentzen know Milo’s significant developmental delays likely stem from a mutation in a gene called KDM1A. He didn’t inherit that mutation from his parents; it’s new in Milo. And because a mutation in that gene is so rare, little is known about it. There is no treatment.\u003c/p>\n\u003cp>If KDM1A is indeed the culprit, Milo has what’s known as a \u003ca href=\"http://www.ncbi.nlm.nih.gov/books/NBK132145/\" target=\"_blank\" rel=\"noopener\">Mendelian disorder\u003c/a>—a rare condition caused by a genetic mutation, typically in a single gene. There are some 7,000-8,000 known Mendelian conditions, but researchers have found the genetic cause for only half. The rest are identified as Mendelian because they are transmitted from parents to children in ways suggesting they are caused by single genes.\u003c/p>\n\u003cp>In some cases—and researchers say Milo’s appears to be one of them—a new mutation reveals a new condition, previously unidentified.\u003c/p>\n\u003cp>\u003c/p>\u003c/div>",
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"content": "\u003cdiv class=\"post-body\">\u003cp>\u003c/p>\n\u003cp>Families with an unidentified genetic illness are lost in an information desert, isolated by protocols that protect research until published, and by health privacy laws that prevent, for example, a genetics lab from connecting two families with the same mutation.\u003c/p>\n\u003cp>The journey of Milo Lorentzen reveals what \u003ca href=\"https://www.bcm.edu/people/view/christian-schaaf-m-d-ph-d/b251d11c-ffed-11e2-be68-080027880ca6\" target=\"_blank\" rel=\"noopener\">Dr. Christian Schaaf\u003c/a>, an assistant professor at \u003ca href=\"https://www.bcm.edu/\" target=\"_blank\" rel=\"noopener\">Baylor College of Medicine\u003c/a>, says are two major inadequacies in genetic medicine—the absence of support for families with undiagnosed illnesses, and the lack of a clearinghouse where families and researchers can find one another.\u003c/p>\n\u003cp>\u003c/p>\u003cp>\u003c/p>\u003cp>“We all worry about the correct diagnosis, and therapy, and management of the disease,” Schaaf says, “but we don’t think enough about the isolation these families feel, about the stress and anxiety that comes with these disorders.”\u003c/p>\n\u003cp>Recently, however, new and cheaper techniques in genetic testing and efforts to connect families to each other and to researchers offer promise of a future less desolate.\u003c/p>\n\u003cp>“There are lots of researchers who might be interested in families with genetic conditions if they knew they existed,” says \u003ca href=\"http://depts.washington.edu/bamshad/\" target=\"_blank\" rel=\"noopener\">Dr. Michael Bamshad\u003c/a>, principle investigator of the \u003ca href=\"http://uwcmg.org/#/\" target=\"_blank\" rel=\"noopener\">University of Washington Center for Mendelian Genomics\u003c/a>.\u003c/p>\n\u003cp>Bamshad is cofounder of \u003ca href=\"https://www.mygene2.org/MyGene2/\">MyGene2\u003c/a>, a website where families, researchers, and clinicians can connect and share information at no cost. The site is a \u003ca href=\"https://www.openscienceprize.org/res/p/finalists/\">finalist\u003c/a> in a National Institutes of Health competition to make scientific information broadly available.\u003c/p>\n\u003cp>\u003cstrong>‘You’re the Other-Other’\u003c/strong>\u003c/p>\n\u003cp>When your child has an undiagnosed genetic disorder, one of life’s hallmarks is a frustrating series of tests yielding no answers.\u003c/p>\n\u003cp>“The first several years of his life was test after test,” says Karen Park, Milo’s mother. “X-rays, MRIs, blood tests, skin biopsies.”\u003c/p>\n\u003cfigure id=\"attachment_174418\" class=\"wp-caption aligncenter\" style=\"max-width: 2048px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg\" alt=\"Milo Lorentzen is learning to read and speak using an alternative language method that incorporates symbols and pictures. He now reads at or above grade level. “He was starting to have behavioral issues until we gave him this method,” says his mother, Karen Park. “Now Milo has a voice.” \" width=\"2048\" height=\"1536\" class=\"size-full wp-image-174418\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school.jpg 2048w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-400x300.jpg 400w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-800x600.jpg 800w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-768x576.jpg 768w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-1180x885.jpg 1180w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-1920x1440.jpg 1920w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/milo-podd-school-960x720.jpg 960w\" sizes=\"(max-width: 2048px) 100vw, 2048px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Milo Lorentzen is learning to read and speak using an alternative language method that incorporates symbols and pictures. “He was starting to have behavioral issues until we gave him this method,” says his mother, Karen Park. “Now Milo has a voice.” \u003ccite>(Marissa Miller)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Milo had a range of symptoms: low muscle tone and a body that lacked strength, making him slow to lift his head or push up off his stomach; and delays in mimicking people and expressing himself. To his doctors, these symptoms suggested many possibilities.\u003c/p>\n\u003cp>“It takes forever; it’s very slow,” Park says. “And when things keep coming back negative, you feel like: My child is getting tortured; I’m not getting any insight out of this; I just feel like giving up.”\u003c/p>\n\u003cp>Many rare disorders affect at least enough families to constitute what Park calls a tribe: parent groups, coping tips, research tools, and fundraising walks.\u003c/p>\n\u003cp>But Milo’s parents were on their own.\u003c/p>\n\u003cp>Researchers know of only two other children in the world who have a genetic mutation similar to Milo’s. In fact, KDM1A is known to be resistant to evolutionary change; a mutation is so rare researchers hardly ever see it in any animal species.\u003c/p>\n\u003cp>“You’re the ‘other-other’ and not just the ‘other,’” Park says.\u003c/p>\n\u003cfigure id=\"attachment_174447\" class=\"wp-caption aligncenter\" style=\"max-width: 720px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174447\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg\" alt=\"Tess Bigelow is six years old and funtions at an 18-month-old level. Recently she walked 100 meters in the Special Olympics.\" width=\"720\" height=\"753\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263.jpg 720w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-400x418.jpg 400w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-574x600.jpg 574w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/Tess-happy-e1464726348263-32x32.jpg 32w\" sizes=\"(max-width: 720px) 100vw, 720px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Tess Bigelow is six years old and funtions at an 18-month-old level. Recently she walked 100 meters in the Special Olympics. \u003ccite>(Bo Bigelow)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Bo Bigelow, whose daughter Tess is one of only 10 people in the world known to have a mutation in a gene called USP7, went five years before he knew there was anyone else with a similar mutation.\u003c/p>\n\u003cp>“These days there are ribbons and awareness weeks for so many diseases,” Bigelow says, “but when yours is ultra-rare, you feel completely isolated. You feel like you’re never going to hear another person say, ‘Us too!’ And being connected to other families changes all that.”\u003c/p>\n\u003cp>\u003cstrong>Pinpointing the Problem\u003c/strong>\u003c/p>\n\u003cp>In 2013, Milo’s parents had his genes sequenced with a relatively new technique called exome sequencing, which streamlines the process by looking only at genes that code for proteins, and not all an individual’s DNA. It was then they learned about Milo’s gene mutation.\u003c/p>\n\u003cp>Still, mutations in KD1MA are so rare that just spotting it didn’t give Milo’s parents a diagnosis.\u003c/p>\n\u003cp>Why not?\u003c/p>\n\u003cp>“We don’t know what most of our genes do,” says geneticist Barry Starr.\u003c/p>\n\u003cfigure id=\"attachment_174450\" class=\"wp-caption alignright\" style=\"max-width: 250px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/DNA-1.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174450\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/DNA-1.jpg\" alt=\"Genes issue instructions to make proteins, which run the functions of our cells. Genes make up 1-2 percent of our DNA.\" width=\"250\" height=\"371\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Genes issue instructions to make proteins, which run the functions of our cells. Genes make up 1-2 percent of our DNA. \u003ccite>(National Institutes of Health)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Genes issue instructions to make proteins that run the functions of a cell. But discovering what any single gene mutation does is complicated.\u003c/p>\n\u003cp>You need to know how the mutation affects the proteins, and how the proteins related to the disease. You also want to know whether the mutation has appeared in other family members who have experienced symptoms.\u003c/p>\n\u003cp>“You’re playing all these games like a detective story,” says Starr, “trying to solve a mystery.”\u003c/p>\n\u003cp>One way to get a diagnosis is by looking at previous research.\u003c/p>\n\u003cp>Dr. Michael Bamshad once found a mutation in a gene called MYLPF in a boy who had no muscles in his foot. Bamshad found a mouse study in which researchers had made a deliberate mutation MYLPF, resulting in a complete lack of skeletal muscle in the rodent. That was enough evidence to conclude the MYLPF gene was involved in the boy’s condition.\u003c/p>\n\u003cp>But sometimes there is no published research.\u003c/p>\n\u003cp>Bigelow says geneticists who told him of Tess’ mutation didn’t know what the USP7 gene did.\u003c/p>\n\u003cp>“We know this is the gene, but we don’t know anything more than that,” says Bigelow.\u003c/p>\n\u003cp>\u003cstrong>Easing the Isolation\u003c/strong>\u003c/p>\n\u003cp>Bigelow put out a beacon to other families who might have the same mutation: \u003ca href=\"http://www.portlandrootsmedia.com/tess-genetic-mystery\" target=\"_blank\" rel=\"noopener\">a website\u003c/a> and social media posts. Remarkably, it took \u003ca href=\"http://ww2.kqed.org/futureofyou/2016/05/10/social-media-uncovers-rare-diagnosis-after-years-of-frustration/\" target=\"_blank\" rel=\"noopener\">less than a day\u003c/a> for a response. Researchers are now examining his daughter’s case, and at their request Bigelow has used his website to find two more families with the same mutation.\u003c/p>\n\u003cp>But it’s a lot slower for families and researchers to search through hundreds of websites and Facebook pages for common ground.\u003c/p>\n\u003cp>\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/My-gene2.png\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"aligncenter size-full wp-image-174459\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2017/05/My-gene2.png\" alt=\"My gene2\" width=\"627\" height=\"264\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/My-gene2.png 627w, https://cdn.kqed.org/wp-content/uploads/sites/13/2017/05/My-gene2-400x168.png 400w\" sizes=\"(max-width: 627px) 100vw, 627px\">\u003c/a>\u003c/p>\n\u003cp>Now Bigelow and Milo Lorentzen’s parents are registered on MyGene2, where roughly 130 families are seeking information on mutations in more than \u003ca href=\"https://www.mygene2.org/MyGene2/genes\" target=\"_blank\" rel=\"noopener\">100 genes\u003c/a>.\u003c/p>\n\u003cp>Bamshad envisions expanding that to tens of thousands of families.\u003c/p>\n\u003cp>“Our major goal is gene discovery and facilitating clinical diagnosis,” he says. “Very quickly, we could identify hundreds of Mendelian conditions and help thousands of families get a diagnosis for rare diseases.”\u003c/p>\n\u003cp>The main stumbling block is money to pay for outreach, Bamshad says. Tens of thousands of exome sequences are siloed at individual labs and clinics around the country. Because of federal privacy laws, the only people who can share those are the families who had them commissioned.\u003c/p>\n\u003cp>“We see lots of families on Facebook who are searching for a diagnosis,” says geneticist \u003ca href=\"https://depts.washington.edu/genediv/directory/jchong\" target=\"_blank\" rel=\"noopener\">Jessica Chong\u003c/a>, MyGene2 cofounder. “It would take time to go search for them and message each one of them to say, ‘We can help you.’”\u003c/p>\n\u003cfigure id=\"attachment_174559\" class=\"wp-caption aligncenter\" style=\"max-width: 718px\">\u003ca href=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg\">\u003cimg loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-174559\" src=\"http://ww2.kqed.org/futureofyou/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg\" alt=\"Tess Bigelow stomps it out on the track where she competed in the Special Olympics.\" width=\"718\" height=\"590\" srcset=\"https://cdn.kqed.org/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230.jpg 718w, https://cdn.kqed.org/wp-content/uploads/sites/13/2016/05/Tess-track-e1464741655230-400x329.jpg 400w\" sizes=\"(max-width: 718px) 100vw, 718px\">\u003c/a>\u003cfigcaption class=\"wp-caption-text\">Tess Bigelow stomps it out on the track where she\u003ca href=\"http://www.portlandrootsmedia.com/strongerpodcast/2016/5/4/68-special-is-an-understatement\" target=\"_blank\" rel=\"noopener\"> prepares to compete \u003c/a>in the Special Olympics. \u003ccite>(Bo Bigelow)\u003c/cite>\u003c/figcaption>\u003c/figure>\n\u003cp>Dr. Christian Schaaf, who’s working with Tess Bigelow’s mutation, says it has typically taken 15-20 years from the time a disease gene has been discovered until the first patients enter clinical trials. He’s hoping new sequencing tools and social outreach can shrink that to seven or eight years.\u003c/p>\n\u003cp>Milo’s parents hope that new research will give them more answers. They found a U.S. lab that’s agreed to grow cell lines from Milo’s and his father’s DNA, and another lab in Europe is looking to run studies using the gene-editing tool CRISPR.\u003c/p>\n\u003cp>If the labs can replicate Milo’s mutation and study its effects, perhaps Karen Park and Peter Lorentzen will learn more about how the mutation leads to his disorder. From there, will some lab be willing to look at developing a treatment? They don’t know.\u003c/p>\n\u003cp>\u003c/p>\u003c/div>",
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