Identifying the gene that causes fibrodysplasia ossificans progressiva (FOP), one of the rarest and most disabling genetic conditions known to humans and a condition that imprisons its childhood victims in a "second skeleton," has been the focus at Penn's Center for Research in FOP and Related Disorders for the past 15 years. This important discovery is relevant, not only for patients with FOP, but also for those with more common skeletal conditions.

Senior authors Eileen M. Shore, PhD, and Frederick S. Kaplan, MD, both from the Penn Department of Orthopaedic Surgery, and their international consortium of colleagues, report their findings in the April 23 advanced online edition of Nature Genetics. "The discovery of the FOP gene is relevant to every condition that affects the formation of bone and every condition that affects the formation of the skeleton," says Kaplan.

The discovery of the FOP gene was the result of painstaking work by the Penn scientists and their colleagues in the International FOP Research Consortium over many years. It involved the identification and clinical examination of multigenerational families, often in remote regions of the world; genome-wide linkage analysis; identification of candidate genes; and finally, the DNA sequencing and analysis of those candidate genes. The team found that FOP is caused by a mutation of a gene for a receptor called ACVR1 in the bone morphogenetic protein-signaling pathway.

Kaplan describes FOP as the "Mount Everest" of genetic skeletal disorders. His lifelong ambition, as he puts it "is to conquer the summit of this daunting mountain range and see this emerging knowledge turned into novel therapies that can dramatically improve the life of these children. This is nothing less than a campaign for physical independence and personal freedom for these kids. If the knowledge helps us to see farther to help others, that will be great, but this work is for and about the children."

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The CDC says in order that the correct diagnosis is made it is important that doctors eliminate any other known illness many which are often treatable, can make a patient feel chronic fatigue, such as alcohol or substance abuse, autoimmune disease, bipolar affective disorders, cancer, chronic mononucleosis, eating disorders, hormonal disorders, hypothyroidism, major depressive disorders, multiple chemical sensitivities, myalgic encephalomyelitis, neurasthenia, obesity, reactions to prescription drugs, schizophrenia, sleep apnea and narcolepsy, subacute infections and fibromyalgia syndrome.

The CDC advises that a patient must satisfy two of the criteria to receive a diagnosis of CFS:

Six months or more of chronic fatigue, which is not connected to any other known medical condition. Have four or more of the following symptoms at the same time: substantial impairment in short-term memory or concentration, sore throat, tender lymph nodes, muscle pain, multi-joint pain without swelling or redness, headaches of a new type, pattern or severity, unrefreshing sleep or post-exertional malaise which lasts over 24 hours when a person feels unwell for longer than 24 hours after exertion

The patient must have had these symptoms (four of them at the same time) for six consecutive months (or recurring very often).

The researchers believe the development may lead to improved diagnosis and treatment of CFS.

The study is published as a series of 14 articles in the April issue of Pharmacogenomics.