- Email: [email protected]
PATERNAL ORIGIN OF THE EXTRA CHROMOSOME IN DOWN'S SYNDROME
1257
Toronto, were shown to contain many more asbestos fibres; indeed Duluth lagged badly behind. Fourthly, seven Canadian beers and four American beers, not to mention many imported wines, were shown to be similarly replete with asbestos fibres. Indeed, as one wag pointed out, were likely to ingest more asbestos from beer than from Duluth water; his remedy was to drink Scotch. And finally it was demonstrated that the average construction worker, working under satisfactory conditions in which the asbestos-fibre count in the ambient air conforms to the recommended standard, swallows fifty times more fibres than does the water-drinking inhabitant of Duluth. Since the ingested fibres in the construction worker have to be deposited first in the respiratory tract, and then later carried to the pharynx by the muco-ciliary escalator and subsequently swallowed, some doubts about the validity of E.P.A.’s charges now exist. The judge decided not to shut down the company until all the evidence had been heard. As a result, the company’s 5000 employees remain at work, while the trial and arguments continue.
Letters to the Editor CHOICE OF SPECIALTY
they
SHORTAGE OF GAS
The only thing that cheers up Cassandras is the realisation that their gloomy prophecies have been proved correct. But it’s not quite so cheering when suddenly you are struck with the shortages. The harvests have been good, and the fall weather almost uncannily good, as if to make up for the ghastliness of the spring weather, but the energy crisis has developed very rapidly. Gasoline is short and likely to be rationed, but it is chlorine gas that has suddenly got short and has been causing concern in health circles, for it is what we rely on to decontaminate our drinking-water; since we spend so much time and trouble contaminating our drinkingwater we need more and more chlorine to decontaminate it. Many authorities have had difficulties in getting supplies, and the purity of our waters is not such that we can view these shortages with equanimity. There have been a number of outbreaks of water-borne disease this summer and fall. But at least there has been a change in the attitude to science in the highest circles here. After originally ignoring the potential contributions of science towards solving the energy crisis, we have been assured that the Government, having made enormous commitments first to weaponry and then to space, are now going to make such commitments to the energy field. It will be interesting to see the talk translated into action. LURE OF THE OCEANS
While the history of the U.S. in modern times starts on the coasts, the middle of the country has always consoled itself that it was, in more senses than one, the heartland of America. It is thus saddening that the heartland has been losing population to the oceanic States, and this applies as much to physicians as to other more or less desirable members of the community. Some geographers have been of physicians to the documenting and analysing the shift " more glamorous communities " of the East and West coasts. It’s quite a movement. California has more Illinoistrained physicians than Illinois itself. It seems that the causes are complex and not just such simple things as sunshine and sailing-which is perhaps just as well, since not much can be done about these factors. But there are it seems two other major factors-one of which is the disproportionate flow of federal funds to the oceanic States. This is accentuated by the second factor-that the Medicaid and Medicare schemes have restricted the play of the open market that there used to be when physicians were dependent on private patients. While perhaps the indigent can’t move to more salubrious areas the aged often can, and do. But we are unlikely to get the aged to shift back, so it seems probable that the situation will continue to develop unfavourably for the heartland.
SIR,-Although the major specialties in hospital practice are actively pursuing the recommendations of the Todd report,l two obvious and as yet unanswered problems remain. At the end of the preregistration year most junior undecided about their ultimate choice of specialty,2 including general practice. Meanwhile, recruitment into the less prominent specialties is inadequate and haphazard. Undergraduate teaching programmes and the lack of flexibility during the preregistration year are largely responsible for this situation. A new type of post has been created at Canterbury, which I hope in some measure meets the needs of the undecided junior doctor. The appointment is a year’s vocational training in hospital medicine, which is a rotating post through the following departments: (1) health-services research unit at the University of Kent; (2) paediatrics, (3) pathology; (4) nuclear medicine, radiology, and radiodoctors
are
therapy ; (5) psychiatry; (6) high-dependency areas (anaesthetics, coronary care, renal unit); (7) geriatrics; (8) neurology; (9) gastroenterology; (10) outpatient departments (dermatology, physical medicine, venereology); (11) a three-month elective period in a desired specialty. The tutors in each department are encouraged to give the incumbent a broad view of each specialty rather than to allow him to become yet another junior member of the department. Each participant is asked to give a written report after three months and at the end of the year. By keeping the programme flexible, this information is used to alter the schedule according to the needs of the individual. Throughout the year, advice regarding duration of attachments and ultimate career preference is available and sought from the departmental tutors. A short study leave is used to cover specialties not available in this group of hospitals, and the attachment to the health-services research unit has been incorporated and retained at the request of the participants. The selection of candidates for these posts has been based on academic ability. However, since the purpose of this project is to increase exposure and recruitment to the less obvious specialties, selection should be made on the needs of the individual rather than the of academic results. As a result of the Canterbury project, two doctors have seen a district general hospital from an entirely new viewpoint, and there are few consultants who share this overall
prospect
experience. It is not suggested that this scheme is the ultimate answer the problems outlined earlier, but it seems that at some stage in medical training this type of programme would be to
appropriate. I thank the South-East Metropolitan Regional Hospital Board and Dr K. Porter for immediate and enthusiastic support of this proiect. Kent and
Canterbury Hospital, Canterbury CT1 3NG.
B. E. CRAWLEY.
PATERNAL ORIGIN OF THE EXTRA CHROMOSOME IN DOWN’S SYNDROME
SiR,—The quinacrine-fluorescence technique has cribed the
syndrome 1. 2.
origin of the
to
as-
chromosome in Down’s maternal meiotic non-disjunction, at the first extra
Royal Commission on Medical Education, 1965-68: Report. Cmnd. 3569. H.M. Stationery Office, 1968. Last, J. M., Stanley, Gillian R. Br. J. med. Educ. 1968, 2, 137.
1258 division in 6 cases 1,2 and the second division in 1 case.3 The extra chromosome in a trisomy-21 abortus was also verified as caused by maternal first-meiotic error.44 We wish to report a case of trisomy 21 due to paternal nondisjunction. The patient was a 2-week-old boy. Both
The father had one 21 with no satellite and one with a very bright satellite. Thus the extra chromosome can be traced to the father. Assuming that no crossover had taken place between the short arms, the abnormal segregation must have occurred during second meiotic division, since this is when the two similar chromatids should separate. There remains the possibility that the father may be mosaic His fibroblasts were not for 21-trisomy/normal cell-lines. examined, but the chromosomes of 1000 lymphocytes were counted as part of another study. Not one cell with an extra 21 was found. His dermatoglyphic indices, calculated by the methods of Walker 11 and Reed et al.,12 lay well within the range for non-monogolism (Walker index9, dermatogram
scores 48-8). A bimodal distribution of maternal ages for patients with Down’s syndrome can be separated into two curves, one centring around a mode of 28-5 years, the other rising to a peak at 45 years.13 Cases falling into the former group are not maternal-age-dependent, and it is in this group that translocations, both inherited and sporadic, figure prominPartial
Q-band karyotypes from father (F), mother (M), and their son (S) with trisomy 21.
parents were 35 years old. The mother had intensely fluorescent satellites on both no. 21 chromosomes, while the father and son showed only one such variant (see figure). Since this pattern was consistent from cell to cell, paternal second-meiotic non-disjunction was the most plausible
explanation. Chromosome Research Unit, Faculty of Science, Hokkaido University,
Sapporo, Japan.
MOTOMICHI SASAKI YUKIKO HARA.
SiR,—Because of the association between high maternal age and mongolism, the maternal origin of the extra chromosome in trisomy-21 patients has been unquestioned. Two cases with a distinct marker chromosome 21-i.e., a deleted short arm (21p -) found in the mother’s karyotype and present in duplicate in the 21-trisomic child provided proof that non-disjunction occurred in the mother’s oocyte.5,6 With the use of the fluorescent banding technique, additional proof has been found in six more cases,’-9 the origin of the extra chromosome in all instances being traceable to the mother. A fourth study of 20 patients was uninformative. 10 In the eight informative cases reported, the mean maternal age is 35, the youngest mother being 32.5 We report here a family in which non-disjunction can be clearly demonstrated to be of paternal origin. A boy with the classical features of 21-trisomy syndrome is the first child of a mother aged 19 and a father aged 24. A younger brother is normal. Neither parent was exposed to any known noxious environmental agent. The mother’s sister, now dead, was mentally retarded., There’ is no history of retardation on the father’s side. The patient’s lymphocytes showed a karyotype with 47 chromosomes, the extra one being a small acrocentric. There was no sign of mosaicism in 40 cells analysed. Fluorescence karyotyping showed three no. 21 chromosomes, two with identical intensely fluorescing satellites on the short arms (see figure) and a third with a very pale satellite. The lymphocytes of both parents had 46 chromosomes with apparently normal banding patterns. One of the mother’s no. 21 chromosomes had a very pale satellite similar to her son’s, and the other had none. 1. Licznerski, G., Lindsten, J. Hereditas, 1972, 70, 153. 2. Robinson, J. A. Lancet, 1973, i, 131. 3. Mutton, B. E. ibid. p. 375. 4. Kajii, T., Niikawa, N. Personal communication. 5. de Grouchy, J. Ann. Genet. 1970, 13, 52. 6. Juberg, R. C., Jones, B. New Engl. J. Med. 1970, 282, 292. 7. Robinson, J. A. Lancet, 1973, i, 131. 8. Mutton, D. E. ibid. p. 375. 9. Licznerski, G., Lindsten, J. Hereditas, 1972, 70, 153. 10. Smith, G. F., Sachdeva, S. Lancet, 1973, i, 487.
G-group chromosomes of the patient and his parents, illustratir.g the paternal origin of the two brightly satellited no. 21 chromosomes in the patient.
ently. Still, the majority are trisomic, as in the agedependent group. There are several possibilities to account for the presence of the trisomics in the maternal-age-independent group. One suggestion is that young mothers of Down’s syndrome patients are prematurely aged, as shown by earlier menarche,14 early greying of the hair,15 higher frequency of thyroid autoantibodies,16or abnormal glucose toleranceY Maternal 18 or paternal 19 mosaicism may also be a cause. An inherited susceptibility to non-disjunction is another possibility. Our case indicates that paternal non-disjunction should not be overlooked as a cause of trisomy in the maternal-age-independent group. to Mrs Elizabeth Byrnes for her technical assistance Dr K. R. Parker for referring the patient and his family to us. This investigation was supported by a grant from the Medical Research Council of Canada.
My thanks
and
to
Department of Pædiatrics, McMaster University, Hamilton, Ontario, Canada.
IRENE A. UCHIDA.
Walker, N. F. J. Pediat. 1957, 50, 19. Reed, T., Borgaonkar, D. S., Conneally, P. M., Yu, P-L., Nance, W. E., Christian, J. C. ibid. 1970, 77, 1024. 13. Penrose, L. S., Smith, G. F. Down’s Anomaly. London, 1966. 14. Berg, J. M., Bavin, J. T. R. J. med. Genet. 1969, 6, 135. 15. Emanuel, I., Sever, L. E., Milham, S., Thuline, H. C. Lancet, 1972, ii, 361. 16. Fialkow, P. J., Uchida, I. A., Hecht, F., Motulsky, A. G. ibid. 1965, ii, 868. 17. Milunsky, A. Am. J. ment. Defic. 1970, 74, 475. 18. Aarskog, D. Acta pœdiat. scand. 1969, 58, 609. 19. Hsu, L. Y. F., Gertner, M, Leitner, E., Hirschhorn, K. Am. J. hum. Genet. 1971, 23, 592.
11. 12.
Toronto, were shown to contain many more asbestos fibres; indeed Duluth lagged badly behind. Fourthly, seven Canadian beers and four American beers, not to mention many imported wines, were shown to be similarly replete with asbestos fibres. Indeed, as one wag pointed out, were likely to ingest more asbestos from beer than from Duluth water; his remedy was to drink Scotch. And finally it was demonstrated that the average construction worker, working under satisfactory conditions in which the asbestos-fibre count in the ambient air conforms to the recommended standard, swallows fifty times more fibres than does the water-drinking inhabitant of Duluth. Since the ingested fibres in the construction worker have to be deposited first in the respiratory tract, and then later carried to the pharynx by the muco-ciliary escalator and subsequently swallowed, some doubts about the validity of E.P.A.’s charges now exist. The judge decided not to shut down the company until all the evidence had been heard. As a result, the company’s 5000 employees remain at work, while the trial and arguments continue.
Letters to the Editor CHOICE OF SPECIALTY
they
SHORTAGE OF GAS
The only thing that cheers up Cassandras is the realisation that their gloomy prophecies have been proved correct. But it’s not quite so cheering when suddenly you are struck with the shortages. The harvests have been good, and the fall weather almost uncannily good, as if to make up for the ghastliness of the spring weather, but the energy crisis has developed very rapidly. Gasoline is short and likely to be rationed, but it is chlorine gas that has suddenly got short and has been causing concern in health circles, for it is what we rely on to decontaminate our drinking-water; since we spend so much time and trouble contaminating our drinkingwater we need more and more chlorine to decontaminate it. Many authorities have had difficulties in getting supplies, and the purity of our waters is not such that we can view these shortages with equanimity. There have been a number of outbreaks of water-borne disease this summer and fall. But at least there has been a change in the attitude to science in the highest circles here. After originally ignoring the potential contributions of science towards solving the energy crisis, we have been assured that the Government, having made enormous commitments first to weaponry and then to space, are now going to make such commitments to the energy field. It will be interesting to see the talk translated into action. LURE OF THE OCEANS
While the history of the U.S. in modern times starts on the coasts, the middle of the country has always consoled itself that it was, in more senses than one, the heartland of America. It is thus saddening that the heartland has been losing population to the oceanic States, and this applies as much to physicians as to other more or less desirable members of the community. Some geographers have been of physicians to the documenting and analysing the shift " more glamorous communities " of the East and West coasts. It’s quite a movement. California has more Illinoistrained physicians than Illinois itself. It seems that the causes are complex and not just such simple things as sunshine and sailing-which is perhaps just as well, since not much can be done about these factors. But there are it seems two other major factors-one of which is the disproportionate flow of federal funds to the oceanic States. This is accentuated by the second factor-that the Medicaid and Medicare schemes have restricted the play of the open market that there used to be when physicians were dependent on private patients. While perhaps the indigent can’t move to more salubrious areas the aged often can, and do. But we are unlikely to get the aged to shift back, so it seems probable that the situation will continue to develop unfavourably for the heartland.
SIR,-Although the major specialties in hospital practice are actively pursuing the recommendations of the Todd report,l two obvious and as yet unanswered problems remain. At the end of the preregistration year most junior undecided about their ultimate choice of specialty,2 including general practice. Meanwhile, recruitment into the less prominent specialties is inadequate and haphazard. Undergraduate teaching programmes and the lack of flexibility during the preregistration year are largely responsible for this situation. A new type of post has been created at Canterbury, which I hope in some measure meets the needs of the undecided junior doctor. The appointment is a year’s vocational training in hospital medicine, which is a rotating post through the following departments: (1) health-services research unit at the University of Kent; (2) paediatrics, (3) pathology; (4) nuclear medicine, radiology, and radiodoctors
are
therapy ; (5) psychiatry; (6) high-dependency areas (anaesthetics, coronary care, renal unit); (7) geriatrics; (8) neurology; (9) gastroenterology; (10) outpatient departments (dermatology, physical medicine, venereology); (11) a three-month elective period in a desired specialty. The tutors in each department are encouraged to give the incumbent a broad view of each specialty rather than to allow him to become yet another junior member of the department. Each participant is asked to give a written report after three months and at the end of the year. By keeping the programme flexible, this information is used to alter the schedule according to the needs of the individual. Throughout the year, advice regarding duration of attachments and ultimate career preference is available and sought from the departmental tutors. A short study leave is used to cover specialties not available in this group of hospitals, and the attachment to the health-services research unit has been incorporated and retained at the request of the participants. The selection of candidates for these posts has been based on academic ability. However, since the purpose of this project is to increase exposure and recruitment to the less obvious specialties, selection should be made on the needs of the individual rather than the of academic results. As a result of the Canterbury project, two doctors have seen a district general hospital from an entirely new viewpoint, and there are few consultants who share this overall
prospect
experience. It is not suggested that this scheme is the ultimate answer the problems outlined earlier, but it seems that at some stage in medical training this type of programme would be to
appropriate. I thank the South-East Metropolitan Regional Hospital Board and Dr K. Porter for immediate and enthusiastic support of this proiect. Kent and
Canterbury Hospital, Canterbury CT1 3NG.
B. E. CRAWLEY.
PATERNAL ORIGIN OF THE EXTRA CHROMOSOME IN DOWN’S SYNDROME
SiR,—The quinacrine-fluorescence technique has cribed the
syndrome 1. 2.
origin of the
to
as-
chromosome in Down’s maternal meiotic non-disjunction, at the first extra
Royal Commission on Medical Education, 1965-68: Report. Cmnd. 3569. H.M. Stationery Office, 1968. Last, J. M., Stanley, Gillian R. Br. J. med. Educ. 1968, 2, 137.
1258 division in 6 cases 1,2 and the second division in 1 case.3 The extra chromosome in a trisomy-21 abortus was also verified as caused by maternal first-meiotic error.44 We wish to report a case of trisomy 21 due to paternal nondisjunction. The patient was a 2-week-old boy. Both
The father had one 21 with no satellite and one with a very bright satellite. Thus the extra chromosome can be traced to the father. Assuming that no crossover had taken place between the short arms, the abnormal segregation must have occurred during second meiotic division, since this is when the two similar chromatids should separate. There remains the possibility that the father may be mosaic His fibroblasts were not for 21-trisomy/normal cell-lines. examined, but the chromosomes of 1000 lymphocytes were counted as part of another study. Not one cell with an extra 21 was found. His dermatoglyphic indices, calculated by the methods of Walker 11 and Reed et al.,12 lay well within the range for non-monogolism (Walker index9, dermatogram
scores 48-8). A bimodal distribution of maternal ages for patients with Down’s syndrome can be separated into two curves, one centring around a mode of 28-5 years, the other rising to a peak at 45 years.13 Cases falling into the former group are not maternal-age-dependent, and it is in this group that translocations, both inherited and sporadic, figure prominPartial
Q-band karyotypes from father (F), mother (M), and their son (S) with trisomy 21.
parents were 35 years old. The mother had intensely fluorescent satellites on both no. 21 chromosomes, while the father and son showed only one such variant (see figure). Since this pattern was consistent from cell to cell, paternal second-meiotic non-disjunction was the most plausible
explanation. Chromosome Research Unit, Faculty of Science, Hokkaido University,
Sapporo, Japan.
MOTOMICHI SASAKI YUKIKO HARA.
SiR,—Because of the association between high maternal age and mongolism, the maternal origin of the extra chromosome in trisomy-21 patients has been unquestioned. Two cases with a distinct marker chromosome 21-i.e., a deleted short arm (21p -) found in the mother’s karyotype and present in duplicate in the 21-trisomic child provided proof that non-disjunction occurred in the mother’s oocyte.5,6 With the use of the fluorescent banding technique, additional proof has been found in six more cases,’-9 the origin of the extra chromosome in all instances being traceable to the mother. A fourth study of 20 patients was uninformative. 10 In the eight informative cases reported, the mean maternal age is 35, the youngest mother being 32.5 We report here a family in which non-disjunction can be clearly demonstrated to be of paternal origin. A boy with the classical features of 21-trisomy syndrome is the first child of a mother aged 19 and a father aged 24. A younger brother is normal. Neither parent was exposed to any known noxious environmental agent. The mother’s sister, now dead, was mentally retarded., There’ is no history of retardation on the father’s side. The patient’s lymphocytes showed a karyotype with 47 chromosomes, the extra one being a small acrocentric. There was no sign of mosaicism in 40 cells analysed. Fluorescence karyotyping showed three no. 21 chromosomes, two with identical intensely fluorescing satellites on the short arms (see figure) and a third with a very pale satellite. The lymphocytes of both parents had 46 chromosomes with apparently normal banding patterns. One of the mother’s no. 21 chromosomes had a very pale satellite similar to her son’s, and the other had none. 1. Licznerski, G., Lindsten, J. Hereditas, 1972, 70, 153. 2. Robinson, J. A. Lancet, 1973, i, 131. 3. Mutton, B. E. ibid. p. 375. 4. Kajii, T., Niikawa, N. Personal communication. 5. de Grouchy, J. Ann. Genet. 1970, 13, 52. 6. Juberg, R. C., Jones, B. New Engl. J. Med. 1970, 282, 292. 7. Robinson, J. A. Lancet, 1973, i, 131. 8. Mutton, D. E. ibid. p. 375. 9. Licznerski, G., Lindsten, J. Hereditas, 1972, 70, 153. 10. Smith, G. F., Sachdeva, S. Lancet, 1973, i, 487.
G-group chromosomes of the patient and his parents, illustratir.g the paternal origin of the two brightly satellited no. 21 chromosomes in the patient.
ently. Still, the majority are trisomic, as in the agedependent group. There are several possibilities to account for the presence of the trisomics in the maternal-age-independent group. One suggestion is that young mothers of Down’s syndrome patients are prematurely aged, as shown by earlier menarche,14 early greying of the hair,15 higher frequency of thyroid autoantibodies,16or abnormal glucose toleranceY Maternal 18 or paternal 19 mosaicism may also be a cause. An inherited susceptibility to non-disjunction is another possibility. Our case indicates that paternal non-disjunction should not be overlooked as a cause of trisomy in the maternal-age-independent group. to Mrs Elizabeth Byrnes for her technical assistance Dr K. R. Parker for referring the patient and his family to us. This investigation was supported by a grant from the Medical Research Council of Canada.
My thanks
and
to
Department of Pædiatrics, McMaster University, Hamilton, Ontario, Canada.
IRENE A. UCHIDA.
Walker, N. F. J. Pediat. 1957, 50, 19. Reed, T., Borgaonkar, D. S., Conneally, P. M., Yu, P-L., Nance, W. E., Christian, J. C. ibid. 1970, 77, 1024. 13. Penrose, L. S., Smith, G. F. Down’s Anomaly. London, 1966. 14. Berg, J. M., Bavin, J. T. R. J. med. Genet. 1969, 6, 135. 15. Emanuel, I., Sever, L. E., Milham, S., Thuline, H. C. Lancet, 1972, ii, 361. 16. Fialkow, P. J., Uchida, I. A., Hecht, F., Motulsky, A. G. ibid. 1965, ii, 868. 17. Milunsky, A. Am. J. ment. Defic. 1970, 74, 475. 18. Aarskog, D. Acta pœdiat. scand. 1969, 58, 609. 19. Hsu, L. Y. F., Gertner, M, Leitner, E., Hirschhorn, K. Am. J. hum. Genet. 1971, 23, 592.
11. 12.