Myotonic dystrophy mutations

Myotonic dystrophy mutations

358 Myotonic dystrophy mutations Myotonic dystrophy, a multisystem autosomal dominant disorder, is the commonest adult form of muscular dystrophy, af...

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358

Myotonic dystrophy mutations Myotonic dystrophy, a multisystem autosomal dominant disorder, is the commonest adult form of muscular dystrophy, affecting at least 1 in 7500 people according to some estimates. Its biochemical basis, however, is unknown. In three papers in Nature, research workers from the UK, USA, the Netherlands, and Sweden report the detection of novel restriction fragments within chromosome band 19ql3.3 that are specific to individuals with myotonic dystrophy. Harley et aP and Johnson, de Jong, and colleagues2,3 found that a two-allele EcoRl polymorphism, detected in normal individuals as a band of 9 to 10 kb, was replaced by a larger fragment (up to 15 kb) in most patients with myotonic dystrophy. Both groups report that the size of the fragment varies within affected families and suggest that the variability of fragment length may explain the wide variation in age of onset and severity of the disease. Unlike most genetic disorders, no case of myotonic dystrophy is known to have arisen from a new mutation, and Harley et al suggest that the almost complete linkage disequilibrium between myotonic dystrophy and a second polymorphism at the same locus indicates that most cases of the disease are descended from one original mutation. A puzzling feature of the disease, is its tendency to become increasingly severe in successive generations. Harley et al suggests that the original mutation may have been a small (< 0.2 kb) insertion or duplication with an inherent ability to expand. Expansion of a DNA repeat is seen in the fragile X syndrome and may prove to be a common mechanism in human genetic disease.’ 1. Harley HG, Brook JD, Rundle SA, et al. Expansion of an unstable DNA region and phenotypic variation m myotonic dystrophy. Nature 1992; 355: 545-46. 2. Buxton J, Shelbourne P, Davies J, et al. Detection of an unstable fragment of DNA specific to individuals with myotonic dystrophy. Nature 1992; 355: 547-48. 3. Aslanidis C, Jansen G, Amemiya C, et al. Cloning of the esential myotonic dystrophy region and mapping of the putative defect. Nature 1992; 355: 548-51.

After 14 years in

ward she was moved to a very special I visited Joanna the other day, the first time since she left us. She is now 52, and her hair has turned grey; she has been in the hospital for 20 years. A ventilator with a dusty cover stood beside her empty bed littered, as in the past, with torrid novels. She had not had any sort of crisis for the past three years, she told me, pressing the control button on her electric chair so as to move forward and touch the wood of her locker. Was she as happy now as she had been at the teaching hospital? She put a deformed arthritic finger to the tracheotomy tube and replied, "It’s not as much fun here, but I have more freedom and go to my sister’s our

hospital for the chronically ill.

every

Sunday".

Was my earlier decision inappropriate? *

England

*

Although readers may view our senior and junior partners as being somewhat removed from the "coalface" of clinical medicine, we do make the occassional foray into the outside world, albeit nervously. The benefit of such excursions is, of course, that one is able to cast an objective eye on the shifting sands of our health service. On a recent visit to a spanking new district general hospital somewhere south of Bedford Square, the very junior partner, who thought himself reasonably well versed in medical abbreviations, found himself flummoxed by a mysterious new arrival: the ECR. Patients either were or weren’t. Their attribution seemed to follow no logical pattern. Age, sex, nurse irritability index, closet smoker, female ward interloper-nothing would fit. But one thing was certain: those patients who were ECR positive tended to linger a little longer on the wards. And then it was revealed. The Extra-Contractual Referral-that prized admission that brings a precious C210 each day to the hospital from the patient’s home health authority-has arrived. Inhospital rehabilitation was of unparalleled excellence.

International

In

*

Diary

Now

Malcolm Dean’s review (Jan 18, p 170) of the Audit Commission’s report on the use of acute medical beds in the NHS mentions "the ultimate in inappropriate treatment-a patient in Ealing who had occupied an acute bed for 10 years, shutting off treatment to roughly 400 potential patients..." Perhaps I am guilty of the same, depending on how one defines "inappropriate". When I became a consultant many years ago at a London teaching hospital, I "inherited" Joanna, who at age 16 had presented to my predecessor with Graves’ disease, which had been cured with subtotal thyroidectomy. Myasthenia gravis later developed (and was not improved by thymectomy) and then more autoimmune mayhem-addisonian anaemia, guttate psoriasis, and rheumatoid arthritis. At my instigation ACTH was tried but made her myasthenia worse; and some years later newly developed prednisolone, canvassed by our senior registrar, did the same. She continued to "live" on neostigmine with regular injections of atropine to offset its side-effects. Most of the time she was "stable" (as the media would now put it), but she was almost bedridden and subject to frequent myasthenic and cholinergic crises, in which she had to have mucus sucked from her lungs, be ventilated through her permanent tracheostomy, and be fed through a Ryle’s tube. The equipment for such emergencies was in constant readiness. There were, to my way of thinking, a number of good reasons for not transferring her to one of the long-stay institutions that existed in those days. She was too young at 24 to share accommodation with elderly, senile, or terminally ill patients; she was near where her husband worked, so that he could visit her two or three times a week; I believed, perhaps erroneously, that she enjoyed the life of the ward-its comings and goings; she "trained" generations of student-nurses in the care of the partially paralysed and the respiratorily compromised patient; she incited the interest and respect of generations of medical students; she was always at risk of a crisis and I thought that an acute ward provided the skills and facilities she needed; and we lived in hope that the new molecular biology would one day provide a cure.

A conference on Extended Clinical Consulting By Hospital Computer Network will be held in Cambridge, Massachusessts, USA, on March 23-25: Marketing Department, New York Academy of Sciences, 2 East 63rd Street, New York, NY 10021, USA (212-838 0230). 1st international workshop entitled Iodine Deficiency in Europe-A Continuing Concern is to take place in Brussels on April 24-28: Secretanat, F Delange, Department of Radioisotopes, Hopital Saint-Pierre, 322 rue Haute, 1000-Brussels, Belgium (32-2-535 45 63). 3rd world congress on Foodborne Infections and Intoxications is to take place in Berlin on June 16-19: Generalsekretariat Weltkongress, c/o Institute of Veterinary Medicine, Robert von Ostertag Institute, Federal Health Office, PO Box 33 00 13, D-1000 Berlin 33, Germany (030-8308

2675). 8th international conference on AI[DSJIH STD World Congress will take place in Amsterdam on July 19-24: Harvard AIDS Institute, 8 Story Street, Cambridge, Massachusetts 02138, USA, or VIII International Conference on AIDS/III STD World Congress, CLB, Plesmaniaan 125, Postbus 9190, 1006 AD Amsterdam, Netherlands. 46th congress entitled General Practice in Europe Without Borders is to be held in Klagenfurt on Sept 7-11: Secretariat, Societas Intemationalis Medicinae Generalis, Bahnhofstrasse 22, A-9020 Klagenfurt, Austria

(0463-55449). 2nd world congress on latrogenic Complications is to take place in on Sept 14-17: Dr 0. Winding, International Society for the Prevention of Iatrogenic Complications, University of Copenhagen, Institute of Forensic Medicine, 11 Fr.d.V’s Vej, DK-2100 Copenhagen, Denmark (45-35 37 32 22 ext 438).

Copenhagen

17th international symposium on Immunology and Blood Transfusion is to take place in Groningen on Sept 23-25: Symposium Secretariat, Red Cross Blood Bank Groningen-Drenthe, PO Box 1191,9701 BD Groningen, Netherlands (telephone and fax 31-50 137777).