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XX CHROMOSOMES AND RENAL AGENESIS
1427 cholesterol diets used for patients with coronary heart-disease. Advice on reducing diets, low-fat diets, high or low protein diets, and low-residue or milk-free diets in ulcerative colitis, as well as much nutritional advice of prophylactic value (for example, to old people and antenatal patients), could all be contributed by dietitians, with very obvious benefit to both patients and general practitioners. A list of members, who are qualified dietitians, is issued by the British Dietetic Association, 251 Brompton Road, London S.W.3; there is also a Dietitians Register containing the names of State-registered dietitians, issued by the Council for Professions Supplementary to Medicine, York House, London Woodville, Helensburgh, Dumbartonshire.
M. C. STEVEN.
XX CHROMOSOMES AND RENAL AGENESIS SIR,-The association of renal agenesis with masculinisation of the external genitalia in females, discussed by Dr. Schlegel and his colleagues (April 9), may occur also as part of the syndrome of cryptophthalmos.1-7 Other features of this malformation complex-apart from the absence of palpebral apertures with disorganisation of the ocular globes which gives the syndrome its name-include middle and outer ear malformations, high or cleft palate, deformity of the larynx, wide separation of the symphysis pubis, displacement of the umbilicus and nipples, syndactyly and other digital malformations, meningoencephaloceles, anal stenosis, and congenital cardiac malformations. All these components may be present in varying degrees or even absent altogether. This is true also of the renal agenesis, and thus the condition may be compatible with life; unilateral loss of renal function was demonstrated radiologically in one such survivor.Even though there may also be unilateral or partial manifestation of the cardinal feature of cryptophthalmos, which may sometimes be represented only by prominent epicanthic folds, it does not seem likely that the case of female pseudohermaphroditism described by Dr. Schlegel and his colleagues and those of Carpentier and Potter8 two which they refer are examples of the cryptophthalmos syndrome. Masculinisation of the external genitalia in females occurs in association with this syndrome as well as with more common types of renal agenesis. Furthermore, since masculinisation occurs even in survivors, the explanation of Dr. Schlegel and his colleagues that it is due to high levels of androgenic hormones in a foetus without an excretory mechanism cannot be accepted-at least with respect to the syndrome of cryptophthalmos. Rather, it should be regarded as only one of a bizarre constellation of defects in embryogenesis found in this syndrome for which a unitary explanation is difficult to find. Autosomal recessive inheritance seems to be involved, reflected by reports of multiple cases within sibships and occasional consanguinity of parents. 3-6 If this is so, the gene concerned should be regarded as sublethal in homozygous form-survival depending on the degree of renal involvement. Masculinisation of the external genitalia in varying degrees occurred in two pairs of sisters56 with this condition. In each sibship one girl survived, while the second members of the pairs died shortly after birth with renal agenesis in one and gross renal hypoplasia in the other. Chromosomal studies in the two survivors, by Dr. J. H. Edwards, revealed normal female karyotypes, despite the fact that one girl was originally brought up as a male. A positive sex-chromatin pattern was recorded in one of the dead girls. In both survivors normal values were found on analysis of urinary 17-ketosteroids; this 8 seems to support the contention of Carpentier and Potter that the types of female pseudohermaphroditism (" non1.
2. 3. 4. 5. 6. 7. 8.
Duke-Elder, S. System of Ophthalmology: vol. III, part 2; p. 829. London, 1964. Brodsky, I., Waddy, G. Med. J. Aust. 1940, i, 894. Ashley, L. M. J. Hered. 1947, 38, 174. Gupta, S. P., Saxena, R. C. Br. J. Ophthal. 1962, 46, 629. Fraser, G. R. Ann. hum. Genet. 1962, 25, 387. Fraser, G. R. J. med. Genet. 1964, 1, 118. Ehlers, N. Acta ophthal. 1966, 44, 84. Carpentier, P. J., Potter, E. L. Am. J. Obstet. Gynec. 1959, 76, 235.
specific ") which are associated with renal agenesis and maldevelopment of other organs may not be due to the hormonal androgenic influences known to be responsible for those types which are not associated with such malformations (" specific pseudohermaphroditism "). It is impossible to be certain of the sex of cases of cryptophthalmos with indeterminate external genital organs, described before the era of nuclear and chromosomal sexing. It as seems to be the case in the more common of renal type agenesis described by Carpentier and Potter8 and by Dr. Schlegel and his colleagues, that such pseudohermaphrodites are all females. One survivor with cryptophthaknos with a normal male karyotype had unequivocally male external cenital orL),ans.7 Department of Genetics, University of Adelaide, G. R. FRAZER. Australia.
may
be, however,
PHYTOHÆMAGGLUTININ AND MOUSE LYMPHOCYTES was SIR,-It disappointing to see Dr. Macario’s interesting letter on mouse lymphocytes (April 9) illustrated with a photograph of what appear to be human chromosomes. The normal mouse complement consists of 40 acrocentric chromosomes. Dr. Macario’s illustration shows 46 chromosomes, some of which appear to have median to submedian centromeres. Medical Research Council, Psychiatric Genetics Research Unit, Institute of Psychiatry,
Maudsley Hospital,
J. KAHN.
London S.E.5.
*** This letter has been shown to Dr. Macario, whose reply follows.-ED. L. SIR,-Ireally cannot understand why the mitosis mentioned resembles the mitosis of human cells in certain aspects. When I re-examined the preparation containing the mitosis shown in the photograph I was not able to find any mitosis where I could see exactly the character and number of the chromosomes. It was therefore impossible to be absolutely clear as to whether there had perhaps been a mistake in the labelling and identification of the preparation before the photograph was taken. It should be stressed that from my present work in the laboratory, I believe that for cytogenetic studies in the mouse the material obtained by direct method from lymph-node, spleen, or thymus is much better than that obtained from lymphocyte culture. Institute for Haematological Investigations, National Academy of Medicine, Buenos Aires, Argentina.
A.
J. L. MACARIO.
PATERNAL ORIGIN OF AN XXYY ANOMALY SiR,łThe X-linked blood-group antigen Xga can give information about the origin of the X chromosomes in gonosomal abnormalities. In some families, for example, the groups showed that the extra X of an XXY son was maternal and in others that it was paternal 1 2; they showed in some families that the single X of an XO daughter was maternal and in others that it was paternal 3; and they showed that all the Xs of two XXXXY males were of maternal origin.4 De la Chapelle et al.5 have reported a family in which the Xg groups showed that an XXYY son had an X as well as two Ys which were of paternal orisin. A second such case is here recorded. Frøland, A., Johnsen, S. G., Andresen, P., Dein, E., Sanger, R., Race, R. R. Lancet, 1963, ii, 1121. 2. Ferguson-Smith, M. A., Mack, W. S., Ellis, P. M., Dickson, M., Sanger, R., Race, R. R. ibid. 1964, i, 46. 3. Lindsten, J., Bowen, P., Lee, C. S. N., McKusick, V. A., Polani, P. E., Wingate, M., Edwards, J. H., Hamper, J., Tippett, P., Sanger, R., Race, R. R. ibid. 1963, i, 558. 4. Lewis, F. J. W., Frøland, A., Sanger, R., Race, R. R. ibid. 1964, ii, 589. 5. de la Chapelle, A., Hortling, H., Sanger, R., Race, R. R. Cytogenetics, 1964, 3, 334. 1.
M. C. STEVEN.
XX CHROMOSOMES AND RENAL AGENESIS SIR,-The association of renal agenesis with masculinisation of the external genitalia in females, discussed by Dr. Schlegel and his colleagues (April 9), may occur also as part of the syndrome of cryptophthalmos.1-7 Other features of this malformation complex-apart from the absence of palpebral apertures with disorganisation of the ocular globes which gives the syndrome its name-include middle and outer ear malformations, high or cleft palate, deformity of the larynx, wide separation of the symphysis pubis, displacement of the umbilicus and nipples, syndactyly and other digital malformations, meningoencephaloceles, anal stenosis, and congenital cardiac malformations. All these components may be present in varying degrees or even absent altogether. This is true also of the renal agenesis, and thus the condition may be compatible with life; unilateral loss of renal function was demonstrated radiologically in one such survivor.Even though there may also be unilateral or partial manifestation of the cardinal feature of cryptophthalmos, which may sometimes be represented only by prominent epicanthic folds, it does not seem likely that the case of female pseudohermaphroditism described by Dr. Schlegel and his colleagues and those of Carpentier and Potter8 two which they refer are examples of the cryptophthalmos syndrome. Masculinisation of the external genitalia in females occurs in association with this syndrome as well as with more common types of renal agenesis. Furthermore, since masculinisation occurs even in survivors, the explanation of Dr. Schlegel and his colleagues that it is due to high levels of androgenic hormones in a foetus without an excretory mechanism cannot be accepted-at least with respect to the syndrome of cryptophthalmos. Rather, it should be regarded as only one of a bizarre constellation of defects in embryogenesis found in this syndrome for which a unitary explanation is difficult to find. Autosomal recessive inheritance seems to be involved, reflected by reports of multiple cases within sibships and occasional consanguinity of parents. 3-6 If this is so, the gene concerned should be regarded as sublethal in homozygous form-survival depending on the degree of renal involvement. Masculinisation of the external genitalia in varying degrees occurred in two pairs of sisters56 with this condition. In each sibship one girl survived, while the second members of the pairs died shortly after birth with renal agenesis in one and gross renal hypoplasia in the other. Chromosomal studies in the two survivors, by Dr. J. H. Edwards, revealed normal female karyotypes, despite the fact that one girl was originally brought up as a male. A positive sex-chromatin pattern was recorded in one of the dead girls. In both survivors normal values were found on analysis of urinary 17-ketosteroids; this 8 seems to support the contention of Carpentier and Potter that the types of female pseudohermaphroditism (" non1.
2. 3. 4. 5. 6. 7. 8.
Duke-Elder, S. System of Ophthalmology: vol. III, part 2; p. 829. London, 1964. Brodsky, I., Waddy, G. Med. J. Aust. 1940, i, 894. Ashley, L. M. J. Hered. 1947, 38, 174. Gupta, S. P., Saxena, R. C. Br. J. Ophthal. 1962, 46, 629. Fraser, G. R. Ann. hum. Genet. 1962, 25, 387. Fraser, G. R. J. med. Genet. 1964, 1, 118. Ehlers, N. Acta ophthal. 1966, 44, 84. Carpentier, P. J., Potter, E. L. Am. J. Obstet. Gynec. 1959, 76, 235.
specific ") which are associated with renal agenesis and maldevelopment of other organs may not be due to the hormonal androgenic influences known to be responsible for those types which are not associated with such malformations (" specific pseudohermaphroditism "). It is impossible to be certain of the sex of cases of cryptophthalmos with indeterminate external genital organs, described before the era of nuclear and chromosomal sexing. It as seems to be the case in the more common of renal type agenesis described by Carpentier and Potter8 and by Dr. Schlegel and his colleagues, that such pseudohermaphrodites are all females. One survivor with cryptophthaknos with a normal male karyotype had unequivocally male external cenital orL),ans.7 Department of Genetics, University of Adelaide, G. R. FRAZER. Australia.
may
be, however,
PHYTOHÆMAGGLUTININ AND MOUSE LYMPHOCYTES was SIR,-It disappointing to see Dr. Macario’s interesting letter on mouse lymphocytes (April 9) illustrated with a photograph of what appear to be human chromosomes. The normal mouse complement consists of 40 acrocentric chromosomes. Dr. Macario’s illustration shows 46 chromosomes, some of which appear to have median to submedian centromeres. Medical Research Council, Psychiatric Genetics Research Unit, Institute of Psychiatry,
Maudsley Hospital,
J. KAHN.
London S.E.5.
*** This letter has been shown to Dr. Macario, whose reply follows.-ED. L. SIR,-Ireally cannot understand why the mitosis mentioned resembles the mitosis of human cells in certain aspects. When I re-examined the preparation containing the mitosis shown in the photograph I was not able to find any mitosis where I could see exactly the character and number of the chromosomes. It was therefore impossible to be absolutely clear as to whether there had perhaps been a mistake in the labelling and identification of the preparation before the photograph was taken. It should be stressed that from my present work in the laboratory, I believe that for cytogenetic studies in the mouse the material obtained by direct method from lymph-node, spleen, or thymus is much better than that obtained from lymphocyte culture. Institute for Haematological Investigations, National Academy of Medicine, Buenos Aires, Argentina.
A.
J. L. MACARIO.
PATERNAL ORIGIN OF AN XXYY ANOMALY SiR,łThe X-linked blood-group antigen Xga can give information about the origin of the X chromosomes in gonosomal abnormalities. In some families, for example, the groups showed that the extra X of an XXY son was maternal and in others that it was paternal 1 2; they showed in some families that the single X of an XO daughter was maternal and in others that it was paternal 3; and they showed that all the Xs of two XXXXY males were of maternal origin.4 De la Chapelle et al.5 have reported a family in which the Xg groups showed that an XXYY son had an X as well as two Ys which were of paternal orisin. A second such case is here recorded. Frøland, A., Johnsen, S. G., Andresen, P., Dein, E., Sanger, R., Race, R. R. Lancet, 1963, ii, 1121. 2. Ferguson-Smith, M. A., Mack, W. S., Ellis, P. M., Dickson, M., Sanger, R., Race, R. R. ibid. 1964, i, 46. 3. Lindsten, J., Bowen, P., Lee, C. S. N., McKusick, V. A., Polani, P. E., Wingate, M., Edwards, J. H., Hamper, J., Tippett, P., Sanger, R., Race, R. R. ibid. 1963, i, 558. 4. Lewis, F. J. W., Frøland, A., Sanger, R., Race, R. R. ibid. 1964, ii, 589. 5. de la Chapelle, A., Hortling, H., Sanger, R., Race, R. R. Cytogenetics, 1964, 3, 334. 1.