The purpose of this dispatch is to provide a focal point of support and information for family members and persons living in Ireland who have Hereditary Multiple Exostoses (HME) in order to encourage them to share their experiences so that people in general will have a clearer understanding of this rare condition and how challenging affected lives can be. I fully appreciate that some of us are rather difficult to get to open up on so personal a subject. I am not one of those, and I expect after reading the following post you will be inspired to add your own personal experiences, questions and feedback in the”Comments” http://nialljoreilly.com/2012/04/28/hereditary-multiple-exostoses-ireland/#comments section located at the bottom of this post, which is divided into the following sections:
- HME and Me
- What is Hereditary Multiple Exostoses?
- Bony Lump?
- What complications are caused by HME?
- What are the chances of transmitting HME to your children?
- Pain relief?
- HME in Ireland
- Support resources for HME patients and their families
HME and Me
I was about 9 years old, maybe younger, when I first noticed the large tender lump protruding from my left shoulder blade like a Rhino horn. I soon became very self-conscious as the bone protrusions multiplied to cover my legs (femur, tibia, and fibula), arms (humerus, radius, and ulna), shoulder blades, hands, feet, ribs, and pelvis, particularly around the shoulder, elbow, wrist, knee, and ankle joints. My height was affected, as was the form of my arms (bow-shaped, my left arm is shorter than my right) and legs (my knees won’t bend all the way), while I had structural damage to my left elbow and hand. I knew I was different to all my other friends, and with such low self-esteem I certainly felt that way. As a consequence I was a quiet child, not going out to ‘find friends’, and, not wanting to intrude on others, would rather wait for others to invite me.
The surgery started in earnest when I was 13 years old and by the time I was 27 years old 48 of the more irritating lumps had been removed. The leading orthopedic surgeons in Ireland at the time Messrs. Gerry “Gold Fingers” Brady, John Varian, and Jimmy Sheehan all had a go at me in both Saint Michael’s Private Hospital, in Dun Laoghaire, and the Mount Carmel Hospital, over in Churchtown (Dublin), while I have been also referred to orthopedic consultants, ENT consultants and neurologists (medical interns in tow) in Liverpool (UK), Seoul (Korea), Singapore, Malaysia, Hong Kong and mainland China.
In 1990, following an operation to remove a lump from my pelvis, I recall the surgeon’s reassuring words “That’s it, no more operations, the bony lumps wouldn’t grow again“, and that I could now get on with my life. I was 27 years old and I’d gone through more operations, physiotherapy, and recovery periods and overcome more obstacles than anyone should ever have to go through in their entire life. So get on with my life I certainly tried to do, and did.
However, despite leading as active a life as I could, the ever present discomfort, which I guess only a with person with HME can truly identify with, continued and in 2008 I was referred to neurologist Mr. Chris Pidgeon at Dublin‘s Beaumount Hospital. He advised surgery on compressed cervical vertabra caused by atypical spinal curvature on the basis that if I didn’t have such surgery sooner rather than later nerve damage and dysfunction would gradually lead to acute lack of sensation on the left side of my body. At around the same time one of China’s leading ENT experts, Professor Pu Xing Kuan (JiangSu Province Hospital, Department of Oto-Rhino-Laryngology -卜行宽, 江苏省人民医院耳鼻咽喉科卜行宽主任医师) postulated a connection between the bony growths and a marked deterioration in my hearing.
New knowledge gleaned through advances in scientific research demonstrates that the socialisation, fatigue, poor coordination and short concentration span (which contributed to learning disabilities when I was in my teens — I probably set some sort of record as to the amount of times [and number of examination boards] I repeated ‘O’ Level Mathematics) issues I have always tried to come to grips with are neurological symptoms associated with HME, and not just a figment of my imagination.
What is Hereditary Multiple Exostoses?
Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas (MO which is the term designated by the World Health Organisation (WHO)), Multiple Hereditary Osteochondromatosis (MHO), Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis, typically affects children whose growth plates open. First described in 1786 by US surgeon John Hunter, HME is a very rare bone condition in which multiple benign bony cartilage-capped lumps (or exostoses / osteochondromas), which are irregular in size, position and number, grow around areas of active bone growth.
Regarding its source scientists have linked HME with mutations in three genes: EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13; and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear). It seems the majority of HME cases have either HME EXT1 or HME EXT2 mutations, while a small proportion of HME cases are linked to the EXT3 gene.
- Although difficult to be precise, given that people with a mild form of HME may remain undiagnosed, online academic sources point to a HME prevalence rate among more closely studied white populations of about 1 in 75,000 people. Interestingly, with respect to Ireland, much higher prevalence rates have been identified among populations with geographically restricted movement, such as islands like Guam, which has about 100 HME cases per 100.000 people.
- Approximately 50% of people with HME are diagnosed by the time they are three years old
- 5% of newborns that carry an HME gene show some signs at birth
- Though not present at birth, 96% of all cases with HME will show noticeable signs by the time they are 12 years old
- Approximately 70% of people with HME have an exostosis or bone abnormality around the knee
- 6 is the number of exostoses the average person affected with HME will typically develop during his or her life
- Most often affected are long tubular bones, while in 10% of cases the small bones of the hands and feet are also affected, the scapula only in 1% of patients. The spine is involved only in 2%, but it can lead to cord compression.
HME has no cure.
An exotosis is a benign rounded or sharp bone growth at the metaphyseal areas of the long bones. Exostoses start, and continue, growing, for the duration of a child’s development around the growth centres of bones that are near the ends of the bones, which is why lumps tend to grow, or fuse, near the joints. When a person has achieved full skeletal growth, the exostoses are expected to stop growing, which is not to say their tenderness also stops. In fact, far from it. Previously less painful exostoses can become very tender with the wear and tear of age. Moreover, exostoses can also return to the same places from where lumps have been previously extracted, and they may be more painful.
What complications are caused by HME?
HME can be particularly troublesome. Because the exostoses grow around areas of active bone growth, they disrupt the normal growth process, leading to defective growth that causes nerve compression, vascular compromise, inequality of limb length and irritation of adjoining soft tissue, such as skin, nerves, tendons, muscles, and blood vessels. Such is their sensitivity, these cartilage-capped lumps can cause chronic pain and numbness until they are surgically removed, and accidentally bumping them against something solid can be particularly painful.
Exostoses that grow near the ends of long bones may limit the normal range of motion of the joints upon which they encroach. Consequently, people with HME may have a shorter stature than average, with studies of HME patients showing the final height in men typically averaging 170 cm (66 in), while the average height in women is about 160 cm (62 in). Moreover, differential rates of growth between a child’s legs or arms can result in disparities in leg or arm length sometimes reaching 2 cm (1 in) or more. Leg length disparity can result in hip pain and difficulties with walking caused by a slanting of the pelvis.
HME patients may also have bowed arms or legs. Often, the forearm will bow out, or the legs can grow to be “knock-kneed”. While function is usually fairly normal, the bowing can be very troublesome.
Another complication caused by HME is stiffness, particularly in the hands, elbows and hips usually because the lumps block their natural movement.
The most alarming potential HME complication is also one of the rarest, typically occurring after skeletal growth has finished. In less than 1% of cases the benign exostoses can become a cancerous tumor called Chondrosarcoma. Such Chondrosarcoma cases are usually in the 20’s to 50’s age range. Growth and soreness are two key warning signs that a benign tumor has become malignant. If a person with HME notices after they have stopped growing that an exostosis is getting larger or painful he or she should consult their doctor right away. Chondrosarcoma while uncommon (arising in 0.5% to 3% of HME patients) is still something people who have Hereditary Multiple Exostoses must know about. An unnoticed bone malignancy always presents a risk for metastasis (the spreading of cancerous cells elsewhere in the body), which is one of the most dangerous complications of any cancer (For more on Chondrosarcoma check out this YouTube video explanation from Dr. Christopher R. Beauchamp, M.D., Orthopedic Oncology and Adult Reconstruction Surgery, Mayo Clinic https://www.youtube.com/watch?v=SJsXktBnZWI )
Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis is a condition that is passed by the genes of the affected parent to their children. If one parent has the condition, there is a 50% likelihood that any child could also develop Hereditary Multiple Exostoses (HME).
As is my own situation, in 10% to 20% of HME cases a person can develop multiple exostoses with no family history of HME. In medical terms this is referred to as a “spontaneous mutation” indicating a genetic problem arose in that person without being inherited from a parent. Moreover, My two brothers who are both in the 50’s have shown no signs of inheriting this condition.
HME has a 96% penetrance, which means that if the disease is indeed transmitted to a child, he or she will have a 96% chance of actually manifesting the disease, and 4% chance of having the disease but never manifesting it.
While males who have the HME gene tend to exhibit more obvious and severe symptoms than females and are therefore more likely to be diagnosed with HME, males and females are equally likely to inherit HME.
What are the chances of transmitting HME to your children?
A person with HME has a 50% chance of transmitting this condition to his or her children. Male and female are equally likely to be affected. In other words, if it is assumed that 4 children are produced, and one parent is carrier and exhibits the disease, the statistical expectation is for: 2 children normal and 2 children with the disease. This does not mean that children will necessarily be affected; it does mean that each child has a 50:50 chance of inheriting the disorder.
For individuals with HME who are considering starting a family preimplantation genetic screening (PGS) [Note: for further information about PGS refer to the Research section below] and prenatal diagnosis are available to determine if their unborn child has inherited the disease. [First pre-implantation genetic diagnosis pregnancy in Ireland hailed by Cork Fertility Centre as ‘major breakthrough Irish Times 3rd November 2013 http://www.irishtimes.com/news/ireland/irish-news/first-pregnancy-in-ireland-using-new-screening-technique-1.1582427]
Some people with HME never need any treatment. They learn to counterbalance the abnormality or reduced range of motion so they can perform as normally as possible. When abnormality does occur it often develops so slowly that the patient can adjust to it well, while others may require surgical treatment to provide relief.
Surgery (bear in mind modern medicine has really advanced with ongoing technological breakthroughs!), physiotherapy and pain management are currently the only options available to HME patients, and while success varies from patient to patient many continue to struggle with pain, fatigue and mobility problems throughout their lives.
It is not unusual for patients with Hereditary Multiple Exostoses (HME) [Multiple Hereditary Exostoses (MHE), Hereditary Multiple Osteochondromas, Multiple Exostoses, Exostosis Multiplex, Multiple Osseous Exostoses, Multiple Cartilaginous Exostoses], or Diaphyseal aclasis to undergo numerous surgical procedures throughout their lives to remove painful or deforming exostoses, correct limb length discrepancies or improve range of motion.
If an exostoses is painful, pressuring an important structure, visibly unsightly, or is easily knocked, it can be removed by surgical methods. Excision itself is usually a fairly straightforward procedure, some are removed without necessitating an overnight stay in hospital. Once removed, however, as previously mentioned, exostoses can reappear (about 20% – 50% of the time), although they are grow to the same extent as before.
When an exostosis causes a growth deformity, such as bowing, sometimes simply cutting off the lumps at an early stage will let the bone straighten itself out and adapt as the child grows. However, some bowing is so acute that not only must the lumps be removed, but also the bone must be straightened. This can be done either by cutting the bone, remodeling it and then holding it in place while it mends or, if the child is still developing, by altering the rate of growth on one side of the growth plate.
There are a number of options available and an orthopedic doctor should be able advise accordingly.
Pain Relief – Medical Marijuana?
Through gene mapping studies scientists, as previously noted, have linked HME with mutations in three genes: EXT1, which maps to Chromosome 8q24.1; EXT2 which maps to Chromosome 11p13; and EXT3 which maps to the short arm of Chromosome 19 (though its precise location is still unclear).
Continuing research of the HME genes should establish an accurate prevalence for each of the three gene types, thus providing greater insight into the growth of cells, which is really what HME is all about. With such rapid advances in science, particularly in terms of gene mapping, it not inconceivable that such as understanding will sooner rather than later provide the knowledge leading to a tangible treatment for HME.
As it stands, gene mapping can serve as a basis for testing children at risk with HME and the information gleaned from such testing will hopefully lead to the prevention of the development of exostoses and their associated complications. There is good reason for optimism: the day when our doctors are equipped to undertake such testing is near.
HME in Ireland
He occupies pride of place in a specially constructed case at Donegal Museum in Letterkenny, in far-flung rugged North West Ireland, and is a key focus of the Ballyhanna Research Project funded by Ireland’s National Roads Authority (NRA) and involving cross-border collaboration between Queen’s University Belfast and the Institute of Technology in Sligo.
Dating from 1100-1400 ‘Ballyhanna Man‘ was one of 1,200 skeletal remains found by archaeologists around a buried church less than a mile south of Ballyshannon, on the banks of the River Erne, in 2006.
And what make him so interesting is that he is the first intact case of Hereditary Multiple Exostoses (HME) / Diaphyseal Aclasis to have emerged in Irish archaeology and one of the very few in the world.
Research (which is ongoing) evidence so far indicates he was about a young adult of about 25 years old when he died (typical of the mortality rate of the other non-HME male remains excavated at the burial site). Projecting bony lumps were evident on the upper and lower limbs: Two bones on each lower leg were fused together, and he was knock kneed. His arms were bow-shaped, with the left arm noticeably shorter.
Ballyhanna Man’s condition would have meant he suffered from pain was very much disabled, and it’s unlikely he would have survived to such an age without some form of support. He appears to have been afforded the same Christian burial as other remains. Regarding his quality of life, given he would have had HME since childhood, who knows?
Given the congenital nature of HME, osteoarchaeologists are working to establish family ties between Ballyhanna Man among the other remains. The remains of a second, man, young to middle aged adult in his late 30’s to 40’s, exhibiting lumps that would have been less obvious than those which afflicted Ballyhanna Man, were also excavated in the same burial ground. According to researchers radiocarbon dating indicates he died several hundred years before Ballyhanna Man, which may point to the HME gene existing within the group for a considerable period of time.
The hope is that in future advancements in genetics and DNA research will provide evidence regarding how HME has evolved.
[Source / read more: http://www.sceala.com/phpBB2/irish-forums-24992.html]
*In addition to the two skeletal remains uncovered by archaeologists at Ballyhanna, two skeletal remains with indications of HME were uncovered by archaeologists in Dublin: The remains of a young to middle-aged female were excavated from a medieval cemetery at St. Stephen’s Street, while a young adult male, dating back to later early Christian era, was exhumed in Kilshane.
In the study of ancient diseases that is paleopathology given that 4 of the 16 known cases of HME are specific to Ireland, and a further 3 cases specific to England (the remaining 9 ancient cases of HME are located in Jordan, Zimbabwe, Peru, Sweden, Poland and Canada) what is the significance of living on an isolated island? Does this point to a higher prevalence of HME in the UK and Ireland? No prevalence rates for UK and Ireland are available online.
Chloe B’s Tells the Story Behind the Scars
“Mikey” Exostoses Boy
Ruby Page Talks HME
Multiple Hereditary Osteochondromatosis (MHO)* – Suzie’s Story
*Multiple Hereditary Osteochondromatosis is the official World Health Organisation term for HME / MHE
HME and Autism / Asperger Syndrome Linkage? Heparan Sulphate and MHE – Dr. Yu Yamaguchi
- Many parents of children with MHE / HME / MHO frequently observe autism- and Asperger Syndrome like social problems in their children http://www.youtube.com/watch?v=6-EXRt_YL6A
HME and Animals?
Bone Lengthening Surgery?
“….“The bumps themselves are not so much a problem, what tends to cause the issue in children or even in adults is if [the bumps] are causing deformity,” explains Dr. Carmen Brauer, an orthopediatric surgeon with the Alberta Children’s Hospital. “Bone lengthening in the upper extremity is fairly rare compared to the lower extremity, and here at the Alberta Children’s Hospital we hadn’t done any lengthening of the upper extremity,” Dr. Brauer says. A team was assembled to perform the first procedure on Dunbar last June. His bone was cut and a device was implanted to apply tension over time to help the bone to grow. “We slowly distract and the bone then heals under the tension we’re applying. By doing that we can lengthen the bone up to a millimeter a day,” Dr. Brauer explains…….” Source / read more and view the Video: http://globalnews.ca/news/907083/bone-lengthening-surgery-saves-calgary-boy-from-disability/
Dorsal Foot Exostosis
Dorsal foot exostosis is a bony growth on the dorsum (top) of the foot. It can occur where the first metatarsal joint meets the big toe, causing the toe to lose its ability to bend. This is also known as Hallux rigidus (inability to move the joint) or Hallux limitus (limited movement of the big toe). Acute or chronic pain on the top of the foot happens in the morning and as the day progresses, more so the longer a person is standing. Metatarsal Cuneiform Exostoses crop up in the midfoot area, where the first metatarsal shaft meets the cuneiform, while a forefoot version of Haglund’s Deformity is where the throat line of the shoe meeting the foot causes pressure and rubbing which results in the fleshy area behind the toes..
Is that a Bunion or an Exostosis protruding from your foot?
- “A large exostosis was the source of a bunion deformity in a 60-year-old woman. Its unusual clinical and radiographic features were suggestive of a bizarre parosteal osteochondromatous proliferation. However, histologic features were most consistent with a benign osteocartilaginous exostosis…..” Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/11482512
Support Resources for HME patients and their families
USA / International
- The MHE Coalition http://www.mhecoalition.org/ Facebook page appears to be more active: https://www.facebook.com/pages/MHE-Coalition/112229608822423 -Excellent particularly with respect to ongoing research and contributions from medical experts.
- MHE and Me http://www.mheandme.com -A support group for children with MHE / HME, which also publishes a useful handbook [A member of the MHE Coalition].
United Kingdom / International
- Hereditary Multiple Exostoses (HME) Support Group http://www.hmesg.org.uk/ Facebook Page: https://www.facebook.com/pages/HME-Support-Group/129536527204525
- This support group has a very instructive web site and hosts an international notice board.
Netherlands (Dutch and English)
- Hereditaire Multiple Exostosen Lotgenotencontactgroep / HME-MO Vereniging Nederland http://www.hme-mo.nl/
- The Dutch HME-MO Association website provides an all encompassing platform which features an English section.
- Association of Genetic Support of Australia (AGSA) http://www.agsa-geneticsupport.org.au
- Hereditary Multiple Exostoses (HME) support in Australia.
France / Belgium (French)
- L’AMem – Association de la Maladie des Exostoses Multiples http://www.webrankinfo.com/annuaire/site-99760.htm
- This support group offers support for almost 400 families in France (and some also from Belgium)
- Multiple Kartilaginare Exostosen http://www.exostosen.de/cms/front_content.php
- This support group offers a German translation of The MHE and Me Handbook
- Hereditary Multiple Exostoses (HME) and Me http://wp.me/p15Yzr-Mr – Despite evidence of HME occurring in 4 ancient Irish skeletal remains (“Ballyhanna Man“) of only 16 ancient skeletal remains worldwide diagnosed with HME bone growth disorder, Ireland doesn’t have an HME information support group, hence this blog.
- MHE Research Foundation http://www.mheresearchfoundation.org/ - Dedicated to researching for the cure to Hereditary Multiple Exostoses / Multiple Osteochondroma.
- National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/sites/ga?disorder=multiple%20hereditary%20exostoses - Up to date website with detailed information on Hereditary Multiple Exostoses (HME). Includes: * Links to introductory material about Multiple Hereditary Exostoses and genetics. * NCBI Book sections and chapters about Multiple Hereditary Exostoses and genetics. * Recent scientific articles about Multiple Hereditary Exostoses. * Links to resources for screening, genetic testing, and directories of specialists.
- PAPER – Cervical spinal cord compression in hereditary multiple exostoses Abstract- Spinal cord compression is an extremely serious complication of hereditary multiple exostoses (HME). A case of HME with compression of the cervical spinal cord is reported. Complete recovery following surgery was achieved. A review of the relevant literature revealed 51 previous cases of HME with cord/cauda equina compression. Most patients were under 30 years of age with more men affected than women. The family history was positive in 60%. The cervical and thoracic areas were predominantly affected, with the symptoms usually developing slowly. Recovery following surgery is to be expected in the majority of cases. In patients with HME and suffering from neurological symptoms, the possibility of spinal cord compression should be considered. Prompt diagnosis and surgical excision provide the best prognosis. Source / read more: http://www.ncbi.nlm.nih.gov/pubmed/9006779
ONGOING RESEARCH – Call for participants – Gene Mutations and Orthopaedic Symptoms Correlation of Multiple Hereditary Exostoses: Multicentre Project.
Source / read more http://clinicaltrials.gov/show/NCT00474331
- PAPER (Chinese)- Ultrastructural features of hereditary multiple osteochondroma cartilage cap in children Abstract -目的观察儿童遗传性多发性骨软骨瘤（hereditary multiple exostoses, HME）软骨帽的超微结构，为儿童HME超微病理诊断提供可靠依据。方法实验组：切除18例HME患儿肋骨瘤体分离软骨帽；对照组：15例胸廓发育畸形患儿手术矫正切除的肋软骨；分别取其纵、横切面应用扫描电镜和透射电镜观察。结果对照组：冷冻断裂的软骨组织内见少量软骨细胞位于软骨陷窝内，软骨组织表面可见大量散乱、稀疏的胶原纤维；软骨细胞数量不多，细胞表面有少量短小的微绒毛，细胞核形状不规则，细胞质内可见到粗面内质网呈条索样分散在细胞质内，线粒体较小，糖原颗粒呈簇状分布。实验组：冷冻断裂的软骨组织内见大量不规则的软骨陷窝，每个软骨陷窝内均含有软骨细胞，细胞表面有丰富的细胞突起；软骨组织内见大量瘤样细胞增生，聚集分布，细胞核较大，细胞质内可见圆形或椭圆形的线粒体及扩张的粗面内质网；瘤细胞间可见毛细血管，其附近可见明显增多的软骨细胞，软骨细胞体积较对照组增大。结论儿童HME软骨帽的超微结构改变（细胞形态及细胞内部细胞器），不同于正常软骨细胞，可能与儿童HME的遗传、发病、发展、转归因素密切相关。 Source / read more: http://www.cjcep.com/oa/darticle.aspx?type=view&id=201302014
- PAPER – Multiple osteochondromas in the archaeological record: a global review Abstract
…The paper undertakes the ﬁrst synthesis study of the 16 known cases of the condition that have been identiﬁed in the international palaeopathological record. It also includes information derived from two newly discovered cases of the disease in two adult male individuals recovered from the Medieval cemetery at Ballyhanna, Co. Donegal, Ireland. Source / read more: http://www.qub.ac.uk/sites/Ballyhanna/FileStore/Filetoupload,216459,en.pdf
7. PAPER – Hereditary Multiple Exostoses: A Current Understanding of Clinical and Genetic Advances…Recent advances in understanding the molecular and genetic basis of this condition not only offer hope for patients and families with HME, but also offer clues to the underlying basis for the formation of the human musculoskeletal system… Source / read more: http://upoj.org/site/files/v14/v14_09.pdf
8. INFORMATION: Preimplantation genetic screening (PGS)
“In medicine and (clinical) genetics preimplantation genetic diagnosis (PGD or PIGD) (also known as embryo screening) refers to procedures that are performed on embryos prior to implantation, sometimes even on oocytes prior to fertilization. PGD is considered another way to prenatal diagnosis. Its main advantage is that it avoids selective pregnancy termination as the method makes it highly likely that the baby will be free of the disease under consideration. PGD thus is an adjunct to assisted reproductive technology, and requires in vitro fertilization (IVF) [Note: IVF costs around €4,000, with fertility drugs, if required, costing up to €3,000] to obtain oocytes or embryos for evaluation.
PGD is also now being performed in a disease called Hereditary multiple exostoses (MHE / MO / HME)..
The term preimplantation genetic screening (PGS) is used to denote procedures that do not look for a specific disease but use PGD techniques to identify embryos at risk. PGD is a poorly chosen phrase because, in medicine, to “diagnose” means to identify an illness or determine its cause. An oocyte or early-stage embryo has no symptoms of disease. They are not ill. Rather, they may have a genetic condition that could lead to disease. To “screen” means to test for anatomical, physiological, or genetic conditions in the absence of symptoms of disease. So both PGD and PGS should be referred to as types of embryo screening….” Source / read more: http://library.everyonehealthy.com/library/furthertest/In%20Vitro%20Fertilization%20With%20Preimplantation%20Genetic%20Diagnosis
9. NEW RESEARCH: How gene mutations lead to the abnormal bone growth that is Hereditary Multiple Exostoses (MHE)?
In humans, MHE is caused by a mutation in one of two genes, Ext1 or Ext2. Together, these genes encode an enzyme necessary to produce heparan sulfate—a long sugar chain that facilitates cell signals that direct bone cell growth and proliferation. But when these genes were inactivated in mice just as they are in human MHE patients, the mice failed to develop the symptoms of MHE. This had scientists scratching their heads.
Enter Dr. Yamaguchi and his colleagues, who took a different approach. Instead of knocking out the Ext1 gene in the whole mouse, they targeted the gene only in bone cells. Moreover, they deleted the gene in only a small fraction of these cells. Surprisingly, this minimalistic approach led to a mouse with all the physical manifestations of MHE, such as bony protrusions, short stature and other skeletal deformities.
The new mouse model answered some long-standing questions about MHE. Scientists had gone back and forth on whether the abnormal growths observed in MHE are true tumors or just malformations of the bone. In this study, the protrusions were made up of two cell types. A minority were mutant cells lacking Ext1, but, amazingly, most were normal bone cells. True tumors, in the strictest sense, arise from the proliferation of mutant cells only. Hence, MHE bone protrusions must result from a different – though still very serious – type of growth.
“I have been waiting 13 years for this breakthrough,” said Sarah Ziegler, vice president of The MHE Research Foundation, which has provided seed funding for Dr. Yamaguchi’s research. “My son had more than a 100 of these tumors and has gone through 15 surgeries. When your child has such a debilitating condition, and you know there’s nothing you can do, it’s petrifying. Now we have hope.”
While this study takes MHE research a giant step forward, more questions remain. For one, it is still unknown how a few mutant bone cells can convince normal cells to divide and proliferate abnormally. Researchers hope that this MHE model will help solve that mystery, as well as provide leads for new treatments.
“This new mouse system also provides a platform for screening potential drugs that inhibit bone growths in MHE,” Dr. Yamaguchi explained. “We are currently developing chemical inhibitors to block their formation.”
Source / read more: http://phys.org/news194606781.html
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