Hum. Genet. 50, 339--340 (1979) © by Springer-Verlag 1979
Letters to the Editors
A Note on the X p J. J. Hoo*
Division of Human Genetics, Department of Community Health, University of Auckland, Auckland, New Zealand Pitrinelli et al. (Hum. Genet. 45,351--354) reported the occurrence o f ' g o n a d a l dysgenesis' in a female patient with a karyotype of 46,X,del(X)(p22). This case report seemed to refute the consensus achieved between the hypothetical model of H o o (1975) and the factual scheme of Fraccaro et al. (1977), which stated that a short arm deletion of the X chromosome distal to the band pl 1 would not cause gonadal dysgenesis (Hoo, 1979). However, a scrutiny of the report published by Pitrinelli et al. reveals that the term gonadal dysgenesis has been incorrectly applied to their patient. Gonadal dysgenesis is characterized by primary amenorrhea, streak gonads, and elevated gonadotropins; but in the patient described by Pitrinelli et al. menarche occurred at age 14 and she continued to menstruate, even though menstruation was very irregular and scanty. Her left gonad was found to be rather small, but apparently not fibrotic or streak-like. Moreover, her plasma gonadotropins were low instead of elevated, as in cases of gonadal dysgenesis. Therefore, it is misleading to refer to the above patient as a case of gonadal dysgenesis. Unfortunately, the clinical data presented in the report were too sparse to allow further comment on the case.
Nevertheless, the authors have made a very important observation, namely, that two of sixty metaphases demonstrated late replication of the normal X chromosome. It is quite possible that other tissues with longer cell cycles than the peripheral lymphocytes might show higher percentages of cells in which the normal X chromosome is inactivated. These latter cells are functionally partially nullisomic for the short arm of the X chromosome (or partially monosomic for segment A according to H o o ' s model). As has been pointed out by the authors, these cells may account for the clinical features of their patient. Hitherto it has been generally assumed that in female patients with X p - the chromosome inactivated will always be the deleted X. This is well accepted on the grounds of selection mechanisms. Those cells in which the normal X chromosome Institut for Humangenetik, Universitfit Hamburg, D-2000 Hamburg 54, Butenfeld 32, Federal Republic of Germany
* P r e s e n t address:
0340-6717/79/0050/0339/$ 01.00
340
J. J, Hoo
has been r a n d o m l y inactivated are functionally partially nullisomic for the short arm o f the X c h r o m o s o m e (or partial m o n o s o m i c for segment A of H o o ' s model), and this partial nullisomy (or partial m o n o s o m y ) is a disadvantageous factor in the process of selection. Therefore, the somatic ceils observed were only those in which the deleted X c h r o m o s o m e was inactivated (Giraud et al., 1974; BartschS a n d h o f f et al., 1976; Kaiser et al., 1976; Fraccaro et al., 1977). N o w , however, the observation of Pitrinelli et al. has shown that the selection mechanism is not 100% effective. Those cells in which the normal X c h r o m o s o m e is inactivated are still viable, especially, if the deleted portion is small (e.g., at p22; see also Tiepolo et al., 1977). There is therefore a 'functional mosaicism', one cell p o p u l a t i o n having the n o r m a l X c h r o m o s o m e inactivated and the other having the deleted X c h r o m o s o m e inactivated. In the tissues with slower cell division rates, the percentage of the disadvantaged cells might be higher than in the peripheral lymphocytes, and this different degree of functional mosaicism m a y account for the differences in the clinical features o f female patients with X p b e y o n d p l 1.
References Bartsch-Sandhoff, M., Terinde, R., Wiegelmann, W., Scholz, W.: Karyotyp-Phenotyp-Korrelation bei einem 46,X,del(X)(p22)-Befund. Hum. Genet. 31, 263--270 (1976) Fraccaro, M., Maraschio, P., Pasquali, F., Scappaticci, S.: Women heterozygous for deficiency of the (p21~pter) region of the X chromosome are fertile. Hum. Genet. 39,283--292 (1977) Giraud, F., Hartung, M., Mattei, J.-F., Bachelet, Y., Mattei, M. G.: D616tion partielle du bras court d'un chromosome X. Arch. Fr. Pediatr. 31,717--724 (1974) Hoo, J. J.: Cytogenetic evidence for evolution of X chromosome inactivation. Lancet 1975I, 1299--1300 Hoo, J. J.: Clinical consequence of Xp-. Hum, Genet. 46,349--351 (1979) Kaiser, P., Zabel, B., Hansen, S., Daume, E.:Short arm deletion of an X chromosome, 46,XXp-. Hum. Genet. 32, 89--100 (1976) Pitrinelli, P., Antonelli, A., Gabellini, P., Gigliani, F., Marcucci, L., Nicoletti, B.: Partial deletion of the X chromosome in gonadal dysgenesis 46,X,del(X)(p22)identified by BUdR treatment. Hum. Genet. 45, 351--354 (1978) Tiepolo, L., Zuffardi, O., Rodewald, A.: Nullisomy for the distal portion of Xp in a male child with X/Y translocation. Hum. Genet. 39,277--281 (1977) Received April 12, 1979
Letters to the Editors
A Note on the X p J. J. Hoo*
Division of Human Genetics, Department of Community Health, University of Auckland, Auckland, New Zealand Pitrinelli et al. (Hum. Genet. 45,351--354) reported the occurrence o f ' g o n a d a l dysgenesis' in a female patient with a karyotype of 46,X,del(X)(p22). This case report seemed to refute the consensus achieved between the hypothetical model of H o o (1975) and the factual scheme of Fraccaro et al. (1977), which stated that a short arm deletion of the X chromosome distal to the band pl 1 would not cause gonadal dysgenesis (Hoo, 1979). However, a scrutiny of the report published by Pitrinelli et al. reveals that the term gonadal dysgenesis has been incorrectly applied to their patient. Gonadal dysgenesis is characterized by primary amenorrhea, streak gonads, and elevated gonadotropins; but in the patient described by Pitrinelli et al. menarche occurred at age 14 and she continued to menstruate, even though menstruation was very irregular and scanty. Her left gonad was found to be rather small, but apparently not fibrotic or streak-like. Moreover, her plasma gonadotropins were low instead of elevated, as in cases of gonadal dysgenesis. Therefore, it is misleading to refer to the above patient as a case of gonadal dysgenesis. Unfortunately, the clinical data presented in the report were too sparse to allow further comment on the case.
Nevertheless, the authors have made a very important observation, namely, that two of sixty metaphases demonstrated late replication of the normal X chromosome. It is quite possible that other tissues with longer cell cycles than the peripheral lymphocytes might show higher percentages of cells in which the normal X chromosome is inactivated. These latter cells are functionally partially nullisomic for the short arm of the X chromosome (or partially monosomic for segment A according to H o o ' s model). As has been pointed out by the authors, these cells may account for the clinical features of their patient. Hitherto it has been generally assumed that in female patients with X p - the chromosome inactivated will always be the deleted X. This is well accepted on the grounds of selection mechanisms. Those cells in which the normal X chromosome Institut for Humangenetik, Universitfit Hamburg, D-2000 Hamburg 54, Butenfeld 32, Federal Republic of Germany
* P r e s e n t address:
0340-6717/79/0050/0339/$ 01.00
340
J. J, Hoo
has been r a n d o m l y inactivated are functionally partially nullisomic for the short arm o f the X c h r o m o s o m e (or partial m o n o s o m i c for segment A of H o o ' s model), and this partial nullisomy (or partial m o n o s o m y ) is a disadvantageous factor in the process of selection. Therefore, the somatic ceils observed were only those in which the deleted X c h r o m o s o m e was inactivated (Giraud et al., 1974; BartschS a n d h o f f et al., 1976; Kaiser et al., 1976; Fraccaro et al., 1977). N o w , however, the observation of Pitrinelli et al. has shown that the selection mechanism is not 100% effective. Those cells in which the normal X c h r o m o s o m e is inactivated are still viable, especially, if the deleted portion is small (e.g., at p22; see also Tiepolo et al., 1977). There is therefore a 'functional mosaicism', one cell p o p u l a t i o n having the n o r m a l X c h r o m o s o m e inactivated and the other having the deleted X c h r o m o s o m e inactivated. In the tissues with slower cell division rates, the percentage of the disadvantaged cells might be higher than in the peripheral lymphocytes, and this different degree of functional mosaicism m a y account for the differences in the clinical features o f female patients with X p b e y o n d p l 1.
References Bartsch-Sandhoff, M., Terinde, R., Wiegelmann, W., Scholz, W.: Karyotyp-Phenotyp-Korrelation bei einem 46,X,del(X)(p22)-Befund. Hum. Genet. 31, 263--270 (1976) Fraccaro, M., Maraschio, P., Pasquali, F., Scappaticci, S.: Women heterozygous for deficiency of the (p21~pter) region of the X chromosome are fertile. Hum. Genet. 39,283--292 (1977) Giraud, F., Hartung, M., Mattei, J.-F., Bachelet, Y., Mattei, M. G.: D616tion partielle du bras court d'un chromosome X. Arch. Fr. Pediatr. 31,717--724 (1974) Hoo, J. J.: Cytogenetic evidence for evolution of X chromosome inactivation. Lancet 1975I, 1299--1300 Hoo, J. J.: Clinical consequence of Xp-. Hum, Genet. 46,349--351 (1979) Kaiser, P., Zabel, B., Hansen, S., Daume, E.:Short arm deletion of an X chromosome, 46,XXp-. Hum. Genet. 32, 89--100 (1976) Pitrinelli, P., Antonelli, A., Gabellini, P., Gigliani, F., Marcucci, L., Nicoletti, B.: Partial deletion of the X chromosome in gonadal dysgenesis 46,X,del(X)(p22)identified by BUdR treatment. Hum. Genet. 45, 351--354 (1978) Tiepolo, L., Zuffardi, O., Rodewald, A.: Nullisomy for the distal portion of Xp in a male child with X/Y translocation. Hum. Genet. 39,277--281 (1977) Received April 12, 1979
