186 gion" (Therman et al. 1990): however, the occurrence of a breakpoint in this region is not inevitably followed by gonadal dysgenesis, nor is infertility exclusively confined to translocations with breakpoints in this region. The "critical region" would perhaps be more appropriately termed a "hotspot for infertility", at least until more data is available from regions such as Xq23 and Xq24 with only three recorded translocations with breaks in each area (Therman et al. 1990). Mittwoch (1975) has suggested that cell n u m b e r or the rate of cell division may be critical for the differentiation of sex organs and, although it seems likely that gene dosage effects are the most important causes of ovarian dysgenesis in individuals with abnormal X chromosomes, cell death might also be a contributory factor. Since the majority of X chromosome rearrangements are associated with cell selection, one might expect both cell death and abnormal dosage effects to influence the phenotype.
References Keitges EA, Plainer CG, Weaver D (1982) Pericentric inversion in dizygotic twins who differ in X chromosome inactivation and menstrual cycle function. Hum Genet 62 : 210-213 Matthei MG. Matthei JF, Ayme S, Giraud F (1982) X-autosome translocations. Hum Genet 61:295-309 Mittwoch U (1975) Chromosomes and sex differentiation. In: Reinboth R (ed) Intersexuality in the animal kindom. Springer, Berlin Heidelberg NewYork, 438-446 Rastan S (1983) Nonrandom X inactivation in mouse X-autosome translocation embryos - location of the inactivation centre. J Embryol Exp Morphol 78 : 1-22 Therman E, Susman B (1990) The similarity of phenotypic effects caused by Xp and Xq deletions in the human female: a hypothesis. Hum Genet 85:175-183 Therman E, Laxova R, Susman B (1990) The critical region on the human Xq. Hum Genet 85 : 455-461
Huntington disease in black African populations E. M. Scrimgeour and S. A. Simpson
of the black population suggested a prevalence of 0.06 per 100,000 (Hayden et al. 1980), whereas in northern Tanzania, it was estimated to be 7 per 100,000 (Scrimgeour 1981). More recently, in Zimbabwe, a prevalence rate of of 0.5-1 per 100,000 was obtained for a Bantu population living near the Mozambique border (Scrimgeour and Pfumojena 1992). In other African countries, H D has been described in black families in Kenya (Gordon 1935; Harries 1973), Uganda (Hutton 1956). Nigeria (Osuntokon 1973), and Togo (Grunitzky 1991). In Zimbabwe, it was first reported in a black family in 1978, but a positive family history was lacking (Samuels and Gelfand 1978). In Ghana, H D was said to be rare (Haddock 1973). It seems very likely that other loci exist in Africa but are unreported for various reasons (e.g. diagnostic uncertainty, lack of supportive pedigree studies, lack of local genetic resources). H D in these various loci may have arisen by mutation but as almost every part of the continent has been visited by foreign travellers, colonists or merchants from early historical times, introduction of the gene would be plausible in some or all cases. Until now, genetic linkage studies between the H D locus and the D4S10 locus (G8) have not been undertaken in any of the above countries with the exception of South Africa (Greenberg et al. 1991). An effort to initiate such studies in Zimbabwe in 1989 was unsuccessful as the exportation of human biological material was not permitted at that time, and D N A studies could not be done locally. However, it is planned to undertake D N A studies in that country in due course, and also in Tanzania where the availability of the National Huntington's Disease Register (Scrimgeour 1982) would facilitate such an initiative. As Dr. Greenberg states, the advent of predictive testing makes determination of the population-specific frequencies for all polymorphisms in the target area in the respective population groups affected by H D an urgent priority. South Africa appears to be the only African country with a black population that currently has the resources to achieve this. An H D database for other African countries is at present being developed in order to provide information about H D to interested workers, to stimulate identification and documentation of loci of the disease, and ultimately to promote relevant D N A marker studies and predictive testing.
Lanarkshire Health Board, 14 Beckford Street, Hamilton, ML30TA, UK
References Received April 15, 1992
In the most interesting article by Dr. Greenberg and colleagues (Greenberg et al. 1991), there is an assertion that Huntington disease (HD) is u n c o m m o n in African and American Blacks. This may well be true, but as far as African countries generally are concerned, the prevalence of H D in populations of apparently unmixed black ancestry is largely unknown. In South Africa, one study Correspondence to: E. M. Scrimgeour
Gordon HL (1935) Huntington's chorea in an East African. Proc R Soc Med 29 : 1469-1470 Greenberg LJ, Martell RW, Theilman J, Hayden MR. Joubert J (1991) Genetic linkage between Huntington disease and the D4S10 locus in South African families: further evidence against non-allelic heterogeneity. Hum Genet 87 : 701-708 Grunitzky KE, Nonon-Saa K, Gnamey K, Balogou A, Apetc D, Hegbe M, Dumas M (1991) Epidemiologie de la maladie de Huntington en Afrique Noire. (Abstract) Tropical Neurology Congress, Limoges, Sept 26-28 Haddock DRW (1973) Neurological disorders in Ghana. 111:Spillane JD (ed) Tropical neurology. Oxford University Press, London
187 Harries JR (1973) Neurological disorders in Kenya. In: Spillane JD (ed) Tropical neurology. Oxford University Press, London Hayden MR, MacGregor JM, Beighton PH (1980) The prevalence of Huntington's chorea in South Africa. S Afr Med J 58:193196 Hutton PW (1956) Neurological disorders in Uganda. E Aft Med J 33-209-223 Osuntoken BO (1973) Neurological disorders in Nigeria. In: Spillane JD (ed) Tropical neurology. Oxford University Press, London Samuels BL, Gelfand M (1978) Huntington's chorea in a Black Rhodesian family. S Aft Med J 54 : 648-651 Scrimgeour EM (1981) Huntington's disease in Tanzania. J Med Genet 18 : 200-203 Scrimgeour EM (1982) The Huntington's Chorea Register of Tanzania. E Afr Med J 59 : 280-282 Scrimgeour EM, Pfumojena J (1992) Huntington disease in black Zimbabwean families living near the Mozambique border. Am J Med Genet (in press)
(1983) on three families only. These results were not confirmed with the availability of a much greater number of patients (Y. Chamla, unpublished data). Rivera and Dominguez (1991) incomprehensibly call the nomenclature in question again, arguing that the rate of C-anaphases remains unchanged despite a 200-fold increase in colchicine concentration. In fact, this experiment was p e r f o r m e d on my mutant cell lines (Chamla et al. 1980), which turned out to be colchicine resistant (Chamla and B6gueret 1982). The colchicine resistance trait was not observed in the variant patients exhibiting C-anaphases (Chamla 1988a). In this general case, Canaphases nevertheless remain P H A and colchicine dependent. Thus nomenclature tallies with facts. The references to the papers of R u d d et al. (1983), G a b a r r o n et al. (1986) and Madan et al. (1987) are not acceptable for the following reasons: 1. These authors rediscovered C-anaphases, described them as a new feature, termed them P C D and quoted my initial observation (Chamla et al. 1980) as a similar phenomenon.
C-anaphases revised Y. Chamla Laboratoire de Cytogdn6tique, Maternit6, H6pital Pellegrin, F-33076 Bordeaux Cedex, France Received December 20, 1991
I was surprised to read the letter of Rivera and Dominguez (1991), which at first sight appears like a fairly good abstract of my review article (Chamla 1988a). The authors, who even used my own title without authorization, should let us know which part of their p a p e r is a new contribution as c o m p a r e d with my statements. Otherwise, as has b e e n acutely pointed out by Fitch (1988), we should simply propose an unnatural eponymic synonym for C-anaphase, i.e. the Rivera and D o m i n g u e z ' syndrome, since these authors claim that the C-anaphase term is inadequate. H a d the authors actually known my work on the subject, they would have been aware that I did not coin the term (Chamla 1988b), which is fully adequate. An obvious misreading of the references cited reduced Rivera and D o m i n g u e z ' letter to a fallacious abridged version. Briefly: C-anaphases are described as Cd-band positive, referring to the C-dot technique of Eiberg (1974) and premature centromere division (PCD) as Cd-band negative, which is probably true, but has never been investigated in a representative survey. My first observations were made with the CT-banding procedure of Chamla and Ruffi6 (1976), while Fitzgerald's first report (1975) showed C-banded chromosomes. C e n t r o m e r e activity in C-anaphases and P C D has not yet been demonstrated. C-anaphases are presented as an autosomal dominant trait. This was concluded after the study of R u d d et al.
2. During 15 years of research on the subject, I have never observed figures identical to C-anaphases in colchicine-free cultures. The conflicting results from these three laboratories should have been proven by pictures and tables. Lastly, "similar configurations" are neither anaphases nor defined entities, but allowed the publishing of too m a n y confusing papers that for ethical considerations I would not quote.
References Chamla Y (1988a) C-anaphases in lymphocyte cultures versus premature centromere division syndromes. Hum Genet 78:111114 Chamla Y (1988b) C-anaphases rediscovered. Hum Genet 79:93 Chamla Y, B6gueret J (1982) Colchicine resistance in human cell lines. Pleiotropic phenotype and decreased membrane permeability. Hum Genet 61 : 73-75 Chamla Y, Ruffi6 M (1976) Production of C and T bands in human mitotic chromosomes after heat treatment. Hum Genet 34: 213-216 Chamla Y, Roumy M, Lass6gues M, Battin J (1980) Altered sensitivity to colchicine and PHA in human cultured cells. Hum Genet 53 : 249-253 Eiberg H (1974) New selective Giemsa technique for human chromosomes, Cd staining. Nature 248 : 55 Fitch N (1988) The unnatural history of a syndrome. Am J Med Genet 29: 949-950 Fitzgerald PH (1975) A mechanism of X chromosome aneuploidy in lymphocytes of aging women. Humangenetik 28 : 153-158 Gabarron J, Jimenez A, Glover G (1986) Premature centromere division dominantly inherited in a subfertile family. Cytogenet Cell Genet 43 : 69-71 Madan K, Lindhout D, Palan A (1987) Premature centromere division (PCD): a dominantly inherited anomaly. Hum Genet 77 : 193-196 Rivera H, Dominguez MG (1991) C-anaphase versus premature centromere division. Hum Genet 88:124 Rudd NL, Teshima IE, Martin RH, Sisken JE, Weksberg R (1983) A dominantly inherited anomaly: a possible cell division mutant. Hum Genet 65 : 117-121
References Keitges EA, Plainer CG, Weaver D (1982) Pericentric inversion in dizygotic twins who differ in X chromosome inactivation and menstrual cycle function. Hum Genet 62 : 210-213 Matthei MG. Matthei JF, Ayme S, Giraud F (1982) X-autosome translocations. Hum Genet 61:295-309 Mittwoch U (1975) Chromosomes and sex differentiation. In: Reinboth R (ed) Intersexuality in the animal kindom. Springer, Berlin Heidelberg NewYork, 438-446 Rastan S (1983) Nonrandom X inactivation in mouse X-autosome translocation embryos - location of the inactivation centre. J Embryol Exp Morphol 78 : 1-22 Therman E, Susman B (1990) The similarity of phenotypic effects caused by Xp and Xq deletions in the human female: a hypothesis. Hum Genet 85:175-183 Therman E, Laxova R, Susman B (1990) The critical region on the human Xq. Hum Genet 85 : 455-461
Huntington disease in black African populations E. M. Scrimgeour and S. A. Simpson
of the black population suggested a prevalence of 0.06 per 100,000 (Hayden et al. 1980), whereas in northern Tanzania, it was estimated to be 7 per 100,000 (Scrimgeour 1981). More recently, in Zimbabwe, a prevalence rate of of 0.5-1 per 100,000 was obtained for a Bantu population living near the Mozambique border (Scrimgeour and Pfumojena 1992). In other African countries, H D has been described in black families in Kenya (Gordon 1935; Harries 1973), Uganda (Hutton 1956). Nigeria (Osuntokon 1973), and Togo (Grunitzky 1991). In Zimbabwe, it was first reported in a black family in 1978, but a positive family history was lacking (Samuels and Gelfand 1978). In Ghana, H D was said to be rare (Haddock 1973). It seems very likely that other loci exist in Africa but are unreported for various reasons (e.g. diagnostic uncertainty, lack of supportive pedigree studies, lack of local genetic resources). H D in these various loci may have arisen by mutation but as almost every part of the continent has been visited by foreign travellers, colonists or merchants from early historical times, introduction of the gene would be plausible in some or all cases. Until now, genetic linkage studies between the H D locus and the D4S10 locus (G8) have not been undertaken in any of the above countries with the exception of South Africa (Greenberg et al. 1991). An effort to initiate such studies in Zimbabwe in 1989 was unsuccessful as the exportation of human biological material was not permitted at that time, and D N A studies could not be done locally. However, it is planned to undertake D N A studies in that country in due course, and also in Tanzania where the availability of the National Huntington's Disease Register (Scrimgeour 1982) would facilitate such an initiative. As Dr. Greenberg states, the advent of predictive testing makes determination of the population-specific frequencies for all polymorphisms in the target area in the respective population groups affected by H D an urgent priority. South Africa appears to be the only African country with a black population that currently has the resources to achieve this. An H D database for other African countries is at present being developed in order to provide information about H D to interested workers, to stimulate identification and documentation of loci of the disease, and ultimately to promote relevant D N A marker studies and predictive testing.
Lanarkshire Health Board, 14 Beckford Street, Hamilton, ML30TA, UK
References Received April 15, 1992
In the most interesting article by Dr. Greenberg and colleagues (Greenberg et al. 1991), there is an assertion that Huntington disease (HD) is u n c o m m o n in African and American Blacks. This may well be true, but as far as African countries generally are concerned, the prevalence of H D in populations of apparently unmixed black ancestry is largely unknown. In South Africa, one study Correspondence to: E. M. Scrimgeour
Gordon HL (1935) Huntington's chorea in an East African. Proc R Soc Med 29 : 1469-1470 Greenberg LJ, Martell RW, Theilman J, Hayden MR. Joubert J (1991) Genetic linkage between Huntington disease and the D4S10 locus in South African families: further evidence against non-allelic heterogeneity. Hum Genet 87 : 701-708 Grunitzky KE, Nonon-Saa K, Gnamey K, Balogou A, Apetc D, Hegbe M, Dumas M (1991) Epidemiologie de la maladie de Huntington en Afrique Noire. (Abstract) Tropical Neurology Congress, Limoges, Sept 26-28 Haddock DRW (1973) Neurological disorders in Ghana. 111:Spillane JD (ed) Tropical neurology. Oxford University Press, London
187 Harries JR (1973) Neurological disorders in Kenya. In: Spillane JD (ed) Tropical neurology. Oxford University Press, London Hayden MR, MacGregor JM, Beighton PH (1980) The prevalence of Huntington's chorea in South Africa. S Afr Med J 58:193196 Hutton PW (1956) Neurological disorders in Uganda. E Aft Med J 33-209-223 Osuntoken BO (1973) Neurological disorders in Nigeria. In: Spillane JD (ed) Tropical neurology. Oxford University Press, London Samuels BL, Gelfand M (1978) Huntington's chorea in a Black Rhodesian family. S Aft Med J 54 : 648-651 Scrimgeour EM (1981) Huntington's disease in Tanzania. J Med Genet 18 : 200-203 Scrimgeour EM (1982) The Huntington's Chorea Register of Tanzania. E Afr Med J 59 : 280-282 Scrimgeour EM, Pfumojena J (1992) Huntington disease in black Zimbabwean families living near the Mozambique border. Am J Med Genet (in press)
(1983) on three families only. These results were not confirmed with the availability of a much greater number of patients (Y. Chamla, unpublished data). Rivera and Dominguez (1991) incomprehensibly call the nomenclature in question again, arguing that the rate of C-anaphases remains unchanged despite a 200-fold increase in colchicine concentration. In fact, this experiment was p e r f o r m e d on my mutant cell lines (Chamla et al. 1980), which turned out to be colchicine resistant (Chamla and B6gueret 1982). The colchicine resistance trait was not observed in the variant patients exhibiting C-anaphases (Chamla 1988a). In this general case, Canaphases nevertheless remain P H A and colchicine dependent. Thus nomenclature tallies with facts. The references to the papers of R u d d et al. (1983), G a b a r r o n et al. (1986) and Madan et al. (1987) are not acceptable for the following reasons: 1. These authors rediscovered C-anaphases, described them as a new feature, termed them P C D and quoted my initial observation (Chamla et al. 1980) as a similar phenomenon.
C-anaphases revised Y. Chamla Laboratoire de Cytogdn6tique, Maternit6, H6pital Pellegrin, F-33076 Bordeaux Cedex, France Received December 20, 1991
I was surprised to read the letter of Rivera and Dominguez (1991), which at first sight appears like a fairly good abstract of my review article (Chamla 1988a). The authors, who even used my own title without authorization, should let us know which part of their p a p e r is a new contribution as c o m p a r e d with my statements. Otherwise, as has b e e n acutely pointed out by Fitch (1988), we should simply propose an unnatural eponymic synonym for C-anaphase, i.e. the Rivera and D o m i n g u e z ' syndrome, since these authors claim that the C-anaphase term is inadequate. H a d the authors actually known my work on the subject, they would have been aware that I did not coin the term (Chamla 1988b), which is fully adequate. An obvious misreading of the references cited reduced Rivera and D o m i n g u e z ' letter to a fallacious abridged version. Briefly: C-anaphases are described as Cd-band positive, referring to the C-dot technique of Eiberg (1974) and premature centromere division (PCD) as Cd-band negative, which is probably true, but has never been investigated in a representative survey. My first observations were made with the CT-banding procedure of Chamla and Ruffi6 (1976), while Fitzgerald's first report (1975) showed C-banded chromosomes. C e n t r o m e r e activity in C-anaphases and P C D has not yet been demonstrated. C-anaphases are presented as an autosomal dominant trait. This was concluded after the study of R u d d et al.
2. During 15 years of research on the subject, I have never observed figures identical to C-anaphases in colchicine-free cultures. The conflicting results from these three laboratories should have been proven by pictures and tables. Lastly, "similar configurations" are neither anaphases nor defined entities, but allowed the publishing of too m a n y confusing papers that for ethical considerations I would not quote.
References Chamla Y (1988a) C-anaphases in lymphocyte cultures versus premature centromere division syndromes. Hum Genet 78:111114 Chamla Y (1988b) C-anaphases rediscovered. Hum Genet 79:93 Chamla Y, B6gueret J (1982) Colchicine resistance in human cell lines. Pleiotropic phenotype and decreased membrane permeability. Hum Genet 61 : 73-75 Chamla Y, Ruffi6 M (1976) Production of C and T bands in human mitotic chromosomes after heat treatment. Hum Genet 34: 213-216 Chamla Y, Roumy M, Lass6gues M, Battin J (1980) Altered sensitivity to colchicine and PHA in human cultured cells. Hum Genet 53 : 249-253 Eiberg H (1974) New selective Giemsa technique for human chromosomes, Cd staining. Nature 248 : 55 Fitch N (1988) The unnatural history of a syndrome. Am J Med Genet 29: 949-950 Fitzgerald PH (1975) A mechanism of X chromosome aneuploidy in lymphocytes of aging women. Humangenetik 28 : 153-158 Gabarron J, Jimenez A, Glover G (1986) Premature centromere division dominantly inherited in a subfertile family. Cytogenet Cell Genet 43 : 69-71 Madan K, Lindhout D, Palan A (1987) Premature centromere division (PCD): a dominantly inherited anomaly. Hum Genet 77 : 193-196 Rivera H, Dominguez MG (1991) C-anaphase versus premature centromere division. Hum Genet 88:124 Rudd NL, Teshima IE, Martin RH, Sisken JE, Weksberg R (1983) A dominantly inherited anomaly: a possible cell division mutant. Hum Genet 65 : 117-121
