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Founder Effect

By Olivier Uyttebrouck
Copyright © 2009 Albuquerque Journal
Journal Staff Writer

          Kathy Romero can spot a rec8 kid instantly because they all have a striking resemblance to her 19-year-old daughter, Victoria.
For more information
Genetic testing and counseling are available from a variety of providers in New Mexico. For information, call Joanne Milisa Drautz, UNM senior genetic counselor, at 272-0340.
    "You can recognize this a mile away, because they all look alike," Romero said. She once noticed a baby girl with recombinant 8 syndrome riding on an elevator. "She looked just like Victoria as a baby."
        The hallmark facial features include a broad face, wide-set eyes, a boxy chest and thick folds under the eyes. Many also have cleft palates. But the most devastating symptoms are mental retardation, kidney and bowel deformities, and heart defects, which typically kill rec8 kids by age 20.
        Rec8 is also a distinctly New Mexico illness that dates to early Spanish settlement here. It isn't mentioned in the state's history books, but rec8 is as much a part of Mew Mexico's history and society as the Pueblo Revolt or the Penitente Brotherhood.
        In fact, rec8 is one of several genetic illnesses deeply rooted in New Mexico. Others include OPMD, a type of muscular dystrophy, and cavernous cranial malformation, or CCM, a potentially life-threatening brain illness.
        The prevalence of those illnesses here is the result of a genetic phenomenon called "founder effect," which occurs when someone carrying a harmful mutation settles in an isolated region. Generations later, the mutation is widely dispersed among the founder's descendants.
        Rec8 and CCM both are more prevalent in New Mexico than anywhere else in the world. The prevalence of OPMD among New Mexicans is second only to that of French Canadians.
        Founder-effect illnesses certainly aren't unique to New Mexico, said Lori Ballinger, a genetic counselor for the University of New Mexico Cancer Research and Treatment Center.
        "Every ethnic group has their own set of diseases," she said. An example is sickle-cell anemia, which is prevalent among African-Americans. "Almost all populations have some type of genetic predisposition for some illnesses."
        But New Mexico's relative isolation has resulted in highly localized founder-effect illnesses here.
        "We just happen to have a captive, very old population, especially in northern New Mexico," Ballinger said.
        Rec8 may be the most New Mexican of the state's founder-effect illnesses.
        The mutation probably originated with an early settler in northern New Mexico or Colorado's San Luis Valley, said Carol Clericuzio, a University of New Mexico physician who first described the illness in a 1993 article in the American Journal of Medical Genetics.
        "All cardiologists in New Mexico look twice at their Hispanic kids" who are born with severe abnormalities, she said. "A parent from a Hispanic family in northern New Mexico or southern Colorado is a red flag."
        Cardiologists and radiologists here can often spot rec8 instantly. "If the kid is born in another state, doctors figure it out from a chromosome study," Clericuzio said.
        Family crisis
        Victoria Romero is happy girl, when she's feeling well, say her parents, Kathy and Felix Romero. She likes to sing and take showers. She laughs and chatters, though her sentences are rarely longer than a couple of words.
        The Belen High School special education student has beaten long odds.
        "When she was born, they told us she wouldn't live past a year," Kathy Romero said. In that first year, Victoria had two major surgeries to repair heart and kidney defects and a third to implant a shunt to drain fluid from her brain.
        The girl's birth in 1990 set off a crisis in Kathy Romero's family.
        Tests showed Kathy carries a mutation called "inverse8." As an "inverse8 carrier," the mother shows no symptoms of rec8, but a child born to her has a 6 percent chance of having the illness.
        The child of an inverse8 carrier also has a 50 percent chance of inheriting the inverse8 mutation, which makes that child a genetic carrier.
        The discovery also meant that Kathy's eight siblings, all of whom live in and around Española, each had a 50 percent chance of being inverse8 carriers.
        "At first, the family didn't want to deal with it," Felix Romero said. Subsequently, the whole family was tested for the mutation, he said. "If they're going to have kids, they're prepared."
        So far, none of their nieces or nephews has rec8.
        Tracking history
        Rec8 is New Mexico's most devastating founder-effect illness. But others can also have debilitating or deadly consequences.
        OPMD can lead to hip and shoulder muscle weakness that can require the person to use a wheelchair, said Dr. Leslie Morrison, a UNM professor of neurology and pediatrics.
        Morrison knows of 900 OPMD patients in New Mexico, making the prevalence rate here second only to that of French Canada, where the disease has been traced to three French sisters who settled in Quebec City in the early 1600s.
        That has led to the theory that a French fur trapper brought the mutation to New Mexico. But Morrison discounts that because fur trappers were transitory residents here. She believes the founder was a Hispanic settler who arrived in New Mexico in the 1600s.
        "Whoever the genetic founder was, they stayed here," she said. "Those families stayed here in the state for hundreds of years. They prospered. They had cultural isolation, language isolation and some geographic isolation."
        Yet another founder-effect illness, CCM, likely had a similar origin. An estimated 10,000 New Mexicans have inherited CCM, which can cause blood-filled lesions to form in the brain or spinal column. That can lead to stroke-like symptoms or seizures.
        An amniocentesis can identify a fetus with OPMD or CCM if the required genetic test is performed, Morrison said.
        But Morrison does not recommend prenatal genetic testing for OPMD or CCM "because I know a lot of people who are very, very healthy living with these diseases," she said.
        Founder-effect illnesses could promote genealogy as an important medical tool for identifying people who could benefit from emerging therapies.
        "People with genetic conditions are often very interested in their family histories," Morrison said. "It could help us identify people for clinical treatment."
   The Founder Effect
    "Founder effect" occurs when a small group of individuals break away to form a new population, resulting in a loss of genetic variation. Such an event occurred in New Mexico in 1598 when Don Juan de Oñate colonized the upper Rio Grande with an estimated 500 settlers.
    A founder mutation is one that appears in the DNA of at least one of the founders. Over generations, the mutation becomes widely dispersed in the new population. Several illnesses with some prevalence in New Mexico are associated with a founder mutation.
    They include:
    OPMD — oculopharyngeal muscular dystrophy
    Likely founder: A Hispanic immigrant who traveled up the Camino Real to New Mexico, possibly in the early or mid-1600s. A French fur trapper also is a possibility.
    Incidence: At least 900 New Mexicans descended from large, old Hispanic families. Only French Canadians have a higher incidence of OPMD.
    Transmission: An autosomal dominant disease, meaning a child has a 50 percent chance of inheriting the disease from a parent with OPMD.
    Typical onset: Mid-40s or 50s.
    Symptoms: Initial symptoms: ptosis, or droopy eyelids; and dysphagia, or difficulty swallowing. OPMD often results in progressive weakening of hip and shoulder muscles.
    Treatment: No treatment for muscle weakening. Surgery and medicine can treat drooping eyelids and swallowing disorders.
    Prognosis: OPMD is rarely life-shortening. But muscle weakening can be severely crippling.
    Rec8 — Recombinant 8 syndrome
    Likely founder: A Hispanic resident of northern New Mexico, possibly in the 17th century.
    Incidence: One in 30,000 New Mexicans descended from old Hispanic families. The state gets about two new cases each year. Rec8 also is found in Colorado's San Luis Valley.
    Transmission: An unknown number of New Mexicans are "inverse8 carriers" who show no symptoms of rec8. A child born to an inverse8 carrier has a 50 percent chance of inheriting the inverse8 mutation but only a 6 percent chance of having the rec8 illness.
    Symptoms: Life-threatening heart, kidney, brain, bladder and bowel defects all are common. Rec8 kids often are severely retarded and require complete care. They typically die within 20 years of heart problems or other complications.
    Onset: Rec8 babies are born with a wide range of serious birth defects.
    Treatment: Doctors can treat symptoms. Rec8 kids typically require multiple surgeries, particularly for heart defects.
    CCM — Cavernous cranial malformation
    Likely founder: A Hispanic resident of New Mexico who arrived here in the 1700s or earlier.
    Incidence: At least 10,000 New Mexicans have the CCM1 mutation. Familial, or inherited, CCM is more prevalent in New Mexico than anywhere else in the world.
    Transmission: A child has a 50 percent chance of inheriting the mutation from a parent with the mutation.
    Symptoms: CCM can cause raspberry-shaped lesions that form in capillaries in the brain or spinal column. The malformations have the potential to bleed, which can result in headaches, seizures or stroke-like symptoms.
    Onset: The illness is highly individualized. Many people develop symptoms in their 30s and 40s, but the illness can strike in infancy. Others develop brain lesions but avoid debilitating symptoms.
    Treatment: Surgery can sometimes be used to remove lesions and limit their damage. Medications can mitigate epilepsy-like symptoms.

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