Clinical Genetics 1979: 15: 259-266
Turner‘s syndrome with a duplicationdeficiency X chromosome derived from a maternal pericentric inversion X chromosome TOHRUMAEDA~ , MICHIKOOH NO^, MASUMIT A K A D AMASATO ~, NISHIDA~, KAZUKOT S U K I O KA A N D~ HAJIME TQMITA~ 1 Department 2 Department
of Laboratory Medicine and of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan A 31-year-old woman of short stature with severe oligomenorrhea was found to carry a duplication-deficiency X chromosome, 46,X,rec(X)dup q,inv(X)(p22ql l), inherited from her mother who carried a pericentric inversion X chromosome, 46,X,inv(X)(p22qI 1). By a combination of autoradiography and BUdR incorporation, the duplication-deficiency X chromosome was always found to be the inactive and late replicating one. In the cultured fibroblasts with the recombinant X chromosome, some of the cells were seen to have bipartite X chromatin bodies. In the mother with inv(X), the normal and the inverted X chromosome were inactivated at random. Received 15 August, accepted f o r publication 14 September 1978 K e y words: Barr body; duplicationideficiency; pericentric inversion; Turner; X chromosome
anomaly.
Several female carriers of unbalanced X-X translocations have been recorded in the literature. Most of them were de novo occurrences and only one family study has included a clinically normal carrier mother of the chromosomal mosaicism (Kim et al.
1974). Dollman et al. (1972) and Kim et al. (1974) presented two different mechanisms for the origin of the X-X translocation: 1) breakage and rearrangement between two X chromosomes, or 2) a n uneven number of crossings-over in a pericentric inversion loop during the first meiotic division in a preceding generation.
To the authers’ knowledge, the family described here represents the first instance where a maternal X chromosomal pericentric inversion is thought to have given rise t o a duplication-deficient gamete, resulting in an offspring with several stigmata suggestive of Turner’s syndrome. Materials and Methods
Chromosomal analyses of the proband, her parents and one of her siblings were performed on leukocytes cultured from peripheral blood samples. Fibroblast cultures were also initiated from biopsy specimens
0009-9163/79/030259-08 $02,5010 0 1979 Munksgaard, Copenhagen
260
MAEDA,OHNO, TAKADA, NISHIDA,TSUKIOKA AND TOMlTA 2
I
I II 111
@
c]0
normal karyotype
not s t u d i e d 46,X,inv(X) ( p 2 2 q l l ) 46,X,rec(X)dup q,inv()o (p22qll)
Fig. 1. Pedigree of the family.
of skin and gonadal tissues of the proband. Several banding techniques were used for chromosome identification. R-banding was carried out by the BUdR-acridine-orange method (Dutrillaux et al. 1973), G-banding by the trypsin-Giemsa method (Seabright 1972) and C-banding by the method described by Sumner (1972). Tritiated thymidine-labeled metaphase autoradiographs of the proband were prepared to study the replication pattern of X chromosomes. Xchromatin investigations were performed on buccal and vaginal mucosa cells and cultured fibroblasts stained with Papanicolaou.
of 14 years, and her menstrual cycle varied from 30 to 60 days. She had both axillary and pubic hair. Breast development and external genitalia were normal. She had short fourth metacarpals, a barrel-shaped chest and pigmented naevi on her face. Pelvic examination revealed a normal-sized uterus. Endocrinologic examinations were as follows; serum LH was 67.7 mIU/ml, FSH 101.1 mIU/ml, serum estron 30.0 pg/ml, estradiol 7.0 pg/ml, and estriol 5.0 pg/ml. Urinary 17-KS was 2.4 mg/day and urinary 17-OHCS 3.2 mg/day. Laparoscopic examination revealed a normal uterus, normal Fallopian tubes and bilateral white streak gonads in the position of the ovaries. Biopsy of these streaks showed
Case History
The proband, 11-3, was seen at the age of 31 years because of severe oligomenorrhea and a fertility problem. She was born to a 32-year-old father and a 27-year-old mother, and her birthweight was 2250 g. Her mother was not known to have had any miscarriages. The pedigree of the family is shown in Figure 1. At examination her height was 138 cm, and her weight 45 kg. H~~ psychomotor development was normal. She had experienced her first menstrual period at the age
Fig. 2. Barr bodies from diploid fibroblasts rec(X). a: Bipartite Barr body, b: One large Barr body.
with
DUPLICATION-DEFICIENCY X CHROMOSOME
26 1
Fig. 3. G-banded karyotype of the proband.
that germ cells were absent but fibrous stroma were present. Her parents and two siblings were physically normal. Cytogenetic Studies
Proband The incidence of X-chromatin positive cells in both buccal and vaginal mucosa cells was 51% and 47%, respectively. The X-chromatin bodies seemed larger than normal but none seemed to be bipartite in the buccal and vaginal mucosa cells. Analysis of Papanicolaou-stained cultured fibroblasts, however, showed that 11.3% of the cells had
one large X chromatin body and 6.5% of the cells had a bipartite body (Fig. 2). Drumsticks appeared larger than normal and their frequency was 6.0%. Chromosome analyses from peripheral blood cultures could be carried out on several occasions, and biopsy specimens from skin and streak gonads were obtained for fibroblast culture. Essentially all peripheral leukocyte and fibroblast cultures showed a modal number of 46 chromosomes, including one No. 2like chromosome instead of a C-X chromosome. The non-modal cells showed a random loss of chromosomes. On the basis of the trypsin-Giemsa banding, this abnormal
262
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND T O M l T A
The modal chromosome number was 46, including one long acrocentric chromosome instead of a C-X chromosome. This abnormal chromosome was identified as a pericentric inversion of an X chromosome by G-banding analysis (Fig. 7). The break points were located at bands Xp22 and X q l l (Fig. 8 4 . Thus, the karyotype could be described as 46,X,inv(X)(p22qll). Staining by BUdR-acridine-orange revealed that the structurally normal X chromosome
Fig. 4. BUdR-acridine-orange stained X chromosomes. a: Two pairs of X chromosomes from the mother. b: Two pairs of X chromosomes from the proband. (The abnormal X is always placed on the right side.)
No. 2-like chromosome was identified as a chromosome consisting of one nearly complete X chromosome and the major part of the long arm of another X chromosome. The break points can be located in the telomeric region of a short arm of one X chromosome (p22) and close to the centromere of another X chromosome ( q l l ) (Fig. 3). Staining with BUdR-acridine-orange revealed that the abnormal X chromosome was always the inactive and late replicating one (Fig. 4b). This finding was also confirmed by autoradiographic studies (Fig. 5). C-banding revealed two blocks of centric heterochromatin; one around the centromere, and the other at the middle of the long arm (Fig. 6b). Mother The buccal smear showed that 10.5% of the cells contained one X-chromatin body, which was normal in size and morphology. A total of 55 metaphase cells from two peripheral blood cultures were analysed.
Fig. 5. A metaphase plate from the proband with rec(X). a: Autoradiograph. b: ~ ~ ~ Giemsa~ stain,~ ~ t i ~
The rec(X) is indicated by an arrow.
~
~
DUPLICATION-DEFICIENCY X CHROMOSOME
263
Fig. 6. C-banded partial metaphase plates. a: mother. b: proband. Arrows indicate heterochromatin blocks of the abnormal X.
was late replicating in 68% of the cells examined and the pericentric inversion X chromosome in 32% of the cells (Fig. 4a). C-banding revealed interstitial heterochromatin in both chromatids at the middle part of the long arm of the inverted chromosome (Fig. 6a). Discussion
After identification of the inv(X)(p22qll) carried by her mother, the karyotype of the proband could be described as 46,X,rec(X), dup q,inv(X)(p22q11), according to the nomenclature of the Paris Conference (1971).
A crossing over within the inversion loop formed during maternal meiosis would give rise to the two types of recombinant chromosome, as shown in Figure 8b. One recombinant chromosome, as seen in the proband, will have a duplication of the major part of the long arm of the X chromosome (qll-qter) and a deficiency of a very small part at the end of the short arm of the X chromosome (p22-pter). The other will have a duplication of a small part at the end of the short arm of the X chromosome and a deficiency of the major part of the long arm of the X chromosome. Recently Fujimoto et al. (1978) have re-
264
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND TOMlTA
viewed the reported cases of familial pericentric inversions with recombinant offspring including chromosomes 3, 4, 5, 8, 10, 13 and G , but not X chromosome. It is generally accepted that the trisomic condition of the X chromosome has an insignificant phenotypic effect. On the other hand, the monosomic condition of the short arm of the X chromosome is considered to be responsible for the expression of Turner’s stigmata (Ferguson-Smith 1965). Thus, the clinical features, such as short stature, streak gonads, short fourth metacarpals, barrel-shaped chest and pigmented naevi, seen in the proband might be explained by
the monosomy for the very small part of the short arm of the X chromosome. There have been reports of several translocations involving two X chromosomes. Six of the reported cases, as indicated by the literature available to us, have demonstrated that the long arm from one X chromosome was translocated onto the short arm of the other (Quichaud et al. 1971, van den Berghe et al. 1973, Kim et al. 1974, Laurent et al. 1975, Ishitobi et al. 1976, Daly et al. 1977). Therman & Patau (1973) assumed that a Barr body condensation center is located on the proximal part of Xq, and that if an
X Fig. 7. G-banded karyotype of the mother.
inv(x)
DUPLICATION-DEFICIENCY X CHROMOSOME
B
ii”+ rrn a
some, which, however, was not a balanced type (Kristensen e t al. 1975). I n the mother with inv(X), BUdR-acridine-orange analysis demonstrated that the normal and the abnormal X chromosomes were inactivated a t random.
p22 qll
*
invlxl
I
v22
b
265
crossing over
References Berghe, H. van den, J. P. Fryns & C. Soyez (1973). X/X translocation in a patient with Turner’s syndrome. Hum. Genet. 20, 377380. Daly, R. F., K. Patau, E. Therman & G . E. Sarto (1977). Structure and Barr body formation of an Xp+ chromosome with two inactivation centers. Amer. J . rned. Genet. 29, 83-93. Dollrnan, A,, W. Nocke & S. Stengel-Rutkowski (1972). Gonadendysgenesie mit ungewohnlicher Strukturanomalie eines X-Chromosorns (45,X/46,XXq+). Hum. Genet. 14, 285-299. Dutrillaux, B., C. Laurent, J. Couturier & J. Lejeune (1973). Coloration par l’acridine orange de chromosomes prLalablement trait& par le 5-bromodBoxyuridine (BUdR). C . R . Acad. Sci. (Paris) 276, 3 179-3 181. Ferguson-Smith, M. A. (1965). Karyotypephenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. J . med. Genet. 2, 142-155. Fujimoto, A., J. W. Towner, S. B. Turkel & M. G . Wilson (1978). A fetus with recombinant of chromosome 8 inherited from her carrier father. Hum. Genet. 40, 241-248. Ishitobi, K., R. Harada, T. Ninomiya, Y. Santo & Y. Harada (1976). XEX translocation in a girl with gonadal dysgenesis. Yonago Acta rned. 20, 19-27. Kim, H. J., L. Y . F. Hsu & K. Hirschhorn (1974). Familial XEX translocation: t(X;X) (p22;q13). Cytogenet. Cell Genet. 13, 454464. Kristensen, H., U. Friedrich, G . Larsen & A. J. Therkelsen (1975). Structural X-chromosome abnormality in a female with gonadal dysgenesis. Hum. Genet. 26, 133-138. Laurent, C., M. C1. Biemont & B. Dutrillaux (1975). Sur quatre nouveaux cas de translocation du chromosome X chez l’homme. Hum. Genet. 26, 35-46. Paris Conference (1971). Standardization in human cytogenetics. Birth Defects: Original Article Series, Vol. VIII, No. 7.
lnvfx’-Bx recombinants
Fig. 8. Diagram showing process of pericentric inversion in X chromosome (a), and recombinant chromosomes resulting from a crossing over within the inversion loop (b).
abnormal X chromosome has two such centers, a proportion of t h e Barr bodies should be bipartite. In fibroblasts obtained from the proband, some of the cells analysed were found t o have bipartite Barr bodies. The present study provides further evidence in support of their hypothesis. It is well known that structurally abnormal X chromosomes invariably replicate late, f o r m X chromatin, and ar e inactive. These facts were well demonstrated in the observations of the recombinant X chromosome of the proband. Information concerning the replication pattern of the inverted human X chromosome is still limited. We have been able to find one case recorded in the literature of pericentric inversion of human X chromo-
266
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND TOMlTA
Quichaud, J . , J . de Grouchy, M. Vitse, I. Emerit & A. Dubreuil (1971). Syndrome de Turner 45,X/46,XXq+. Ann. Endocrinol. 31, 1153-1 155. Seabright, M. (1972). The use of proteolytic enzymes for the mapping of structural rearrangements in the chromosomes of man. Chromosoma (Berl.) 36, 204-210. Sumner, A. T. (1972). A simple technique for demonstrating centromeric heterochromatin. Exp. Cell Res. 75, 304-306.
Therman. E. & K. Patau (1974). Abnormal X chromosomes in man: Origin, behavior and effects. Hum. Genet. 25, 1-16. Address:
Tohru Maeda, M . D . Department of Laboratory Medicine Kitasato University School of Medicine 1, Asamizodai, Sagamihara, Kanagawa Japan
Turner‘s syndrome with a duplicationdeficiency X chromosome derived from a maternal pericentric inversion X chromosome TOHRUMAEDA~ , MICHIKOOH NO^, MASUMIT A K A D AMASATO ~, NISHIDA~, KAZUKOT S U K I O KA A N D~ HAJIME TQMITA~ 1 Department 2 Department
of Laboratory Medicine and of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan A 31-year-old woman of short stature with severe oligomenorrhea was found to carry a duplication-deficiency X chromosome, 46,X,rec(X)dup q,inv(X)(p22ql l), inherited from her mother who carried a pericentric inversion X chromosome, 46,X,inv(X)(p22qI 1). By a combination of autoradiography and BUdR incorporation, the duplication-deficiency X chromosome was always found to be the inactive and late replicating one. In the cultured fibroblasts with the recombinant X chromosome, some of the cells were seen to have bipartite X chromatin bodies. In the mother with inv(X), the normal and the inverted X chromosome were inactivated at random. Received 15 August, accepted f o r publication 14 September 1978 K e y words: Barr body; duplicationideficiency; pericentric inversion; Turner; X chromosome
anomaly.
Several female carriers of unbalanced X-X translocations have been recorded in the literature. Most of them were de novo occurrences and only one family study has included a clinically normal carrier mother of the chromosomal mosaicism (Kim et al.
1974). Dollman et al. (1972) and Kim et al. (1974) presented two different mechanisms for the origin of the X-X translocation: 1) breakage and rearrangement between two X chromosomes, or 2) a n uneven number of crossings-over in a pericentric inversion loop during the first meiotic division in a preceding generation.
To the authers’ knowledge, the family described here represents the first instance where a maternal X chromosomal pericentric inversion is thought to have given rise t o a duplication-deficient gamete, resulting in an offspring with several stigmata suggestive of Turner’s syndrome. Materials and Methods
Chromosomal analyses of the proband, her parents and one of her siblings were performed on leukocytes cultured from peripheral blood samples. Fibroblast cultures were also initiated from biopsy specimens
0009-9163/79/030259-08 $02,5010 0 1979 Munksgaard, Copenhagen
260
MAEDA,OHNO, TAKADA, NISHIDA,TSUKIOKA AND TOMlTA 2
I
I II 111
@
c]0
normal karyotype
not s t u d i e d 46,X,inv(X) ( p 2 2 q l l ) 46,X,rec(X)dup q,inv()o (p22qll)
Fig. 1. Pedigree of the family.
of skin and gonadal tissues of the proband. Several banding techniques were used for chromosome identification. R-banding was carried out by the BUdR-acridine-orange method (Dutrillaux et al. 1973), G-banding by the trypsin-Giemsa method (Seabright 1972) and C-banding by the method described by Sumner (1972). Tritiated thymidine-labeled metaphase autoradiographs of the proband were prepared to study the replication pattern of X chromosomes. Xchromatin investigations were performed on buccal and vaginal mucosa cells and cultured fibroblasts stained with Papanicolaou.
of 14 years, and her menstrual cycle varied from 30 to 60 days. She had both axillary and pubic hair. Breast development and external genitalia were normal. She had short fourth metacarpals, a barrel-shaped chest and pigmented naevi on her face. Pelvic examination revealed a normal-sized uterus. Endocrinologic examinations were as follows; serum LH was 67.7 mIU/ml, FSH 101.1 mIU/ml, serum estron 30.0 pg/ml, estradiol 7.0 pg/ml, and estriol 5.0 pg/ml. Urinary 17-KS was 2.4 mg/day and urinary 17-OHCS 3.2 mg/day. Laparoscopic examination revealed a normal uterus, normal Fallopian tubes and bilateral white streak gonads in the position of the ovaries. Biopsy of these streaks showed
Case History
The proband, 11-3, was seen at the age of 31 years because of severe oligomenorrhea and a fertility problem. She was born to a 32-year-old father and a 27-year-old mother, and her birthweight was 2250 g. Her mother was not known to have had any miscarriages. The pedigree of the family is shown in Figure 1. At examination her height was 138 cm, and her weight 45 kg. H~~ psychomotor development was normal. She had experienced her first menstrual period at the age
Fig. 2. Barr bodies from diploid fibroblasts rec(X). a: Bipartite Barr body, b: One large Barr body.
with
DUPLICATION-DEFICIENCY X CHROMOSOME
26 1
Fig. 3. G-banded karyotype of the proband.
that germ cells were absent but fibrous stroma were present. Her parents and two siblings were physically normal. Cytogenetic Studies
Proband The incidence of X-chromatin positive cells in both buccal and vaginal mucosa cells was 51% and 47%, respectively. The X-chromatin bodies seemed larger than normal but none seemed to be bipartite in the buccal and vaginal mucosa cells. Analysis of Papanicolaou-stained cultured fibroblasts, however, showed that 11.3% of the cells had
one large X chromatin body and 6.5% of the cells had a bipartite body (Fig. 2). Drumsticks appeared larger than normal and their frequency was 6.0%. Chromosome analyses from peripheral blood cultures could be carried out on several occasions, and biopsy specimens from skin and streak gonads were obtained for fibroblast culture. Essentially all peripheral leukocyte and fibroblast cultures showed a modal number of 46 chromosomes, including one No. 2like chromosome instead of a C-X chromosome. The non-modal cells showed a random loss of chromosomes. On the basis of the trypsin-Giemsa banding, this abnormal
262
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND T O M l T A
The modal chromosome number was 46, including one long acrocentric chromosome instead of a C-X chromosome. This abnormal chromosome was identified as a pericentric inversion of an X chromosome by G-banding analysis (Fig. 7). The break points were located at bands Xp22 and X q l l (Fig. 8 4 . Thus, the karyotype could be described as 46,X,inv(X)(p22qll). Staining by BUdR-acridine-orange revealed that the structurally normal X chromosome
Fig. 4. BUdR-acridine-orange stained X chromosomes. a: Two pairs of X chromosomes from the mother. b: Two pairs of X chromosomes from the proband. (The abnormal X is always placed on the right side.)
No. 2-like chromosome was identified as a chromosome consisting of one nearly complete X chromosome and the major part of the long arm of another X chromosome. The break points can be located in the telomeric region of a short arm of one X chromosome (p22) and close to the centromere of another X chromosome ( q l l ) (Fig. 3). Staining with BUdR-acridine-orange revealed that the abnormal X chromosome was always the inactive and late replicating one (Fig. 4b). This finding was also confirmed by autoradiographic studies (Fig. 5). C-banding revealed two blocks of centric heterochromatin; one around the centromere, and the other at the middle of the long arm (Fig. 6b). Mother The buccal smear showed that 10.5% of the cells contained one X-chromatin body, which was normal in size and morphology. A total of 55 metaphase cells from two peripheral blood cultures were analysed.
Fig. 5. A metaphase plate from the proband with rec(X). a: Autoradiograph. b: ~ ~ ~ Giemsa~ stain,~ ~ t i ~
The rec(X) is indicated by an arrow.
~
~
DUPLICATION-DEFICIENCY X CHROMOSOME
263
Fig. 6. C-banded partial metaphase plates. a: mother. b: proband. Arrows indicate heterochromatin blocks of the abnormal X.
was late replicating in 68% of the cells examined and the pericentric inversion X chromosome in 32% of the cells (Fig. 4a). C-banding revealed interstitial heterochromatin in both chromatids at the middle part of the long arm of the inverted chromosome (Fig. 6a). Discussion
After identification of the inv(X)(p22qll) carried by her mother, the karyotype of the proband could be described as 46,X,rec(X), dup q,inv(X)(p22q11), according to the nomenclature of the Paris Conference (1971).
A crossing over within the inversion loop formed during maternal meiosis would give rise to the two types of recombinant chromosome, as shown in Figure 8b. One recombinant chromosome, as seen in the proband, will have a duplication of the major part of the long arm of the X chromosome (qll-qter) and a deficiency of a very small part at the end of the short arm of the X chromosome (p22-pter). The other will have a duplication of a small part at the end of the short arm of the X chromosome and a deficiency of the major part of the long arm of the X chromosome. Recently Fujimoto et al. (1978) have re-
264
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND TOMlTA
viewed the reported cases of familial pericentric inversions with recombinant offspring including chromosomes 3, 4, 5, 8, 10, 13 and G , but not X chromosome. It is generally accepted that the trisomic condition of the X chromosome has an insignificant phenotypic effect. On the other hand, the monosomic condition of the short arm of the X chromosome is considered to be responsible for the expression of Turner’s stigmata (Ferguson-Smith 1965). Thus, the clinical features, such as short stature, streak gonads, short fourth metacarpals, barrel-shaped chest and pigmented naevi, seen in the proband might be explained by
the monosomy for the very small part of the short arm of the X chromosome. There have been reports of several translocations involving two X chromosomes. Six of the reported cases, as indicated by the literature available to us, have demonstrated that the long arm from one X chromosome was translocated onto the short arm of the other (Quichaud et al. 1971, van den Berghe et al. 1973, Kim et al. 1974, Laurent et al. 1975, Ishitobi et al. 1976, Daly et al. 1977). Therman & Patau (1973) assumed that a Barr body condensation center is located on the proximal part of Xq, and that if an
X Fig. 7. G-banded karyotype of the mother.
inv(x)
DUPLICATION-DEFICIENCY X CHROMOSOME
B
ii”+ rrn a
some, which, however, was not a balanced type (Kristensen e t al. 1975). I n the mother with inv(X), BUdR-acridine-orange analysis demonstrated that the normal and the abnormal X chromosomes were inactivated a t random.
p22 qll
*
invlxl
I
v22
b
265
crossing over
References Berghe, H. van den, J. P. Fryns & C. Soyez (1973). X/X translocation in a patient with Turner’s syndrome. Hum. Genet. 20, 377380. Daly, R. F., K. Patau, E. Therman & G . E. Sarto (1977). Structure and Barr body formation of an Xp+ chromosome with two inactivation centers. Amer. J . rned. Genet. 29, 83-93. Dollrnan, A,, W. Nocke & S. Stengel-Rutkowski (1972). Gonadendysgenesie mit ungewohnlicher Strukturanomalie eines X-Chromosorns (45,X/46,XXq+). Hum. Genet. 14, 285-299. Dutrillaux, B., C. Laurent, J. Couturier & J. Lejeune (1973). Coloration par l’acridine orange de chromosomes prLalablement trait& par le 5-bromodBoxyuridine (BUdR). C . R . Acad. Sci. (Paris) 276, 3 179-3 181. Ferguson-Smith, M. A. (1965). Karyotypephenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. J . med. Genet. 2, 142-155. Fujimoto, A., J. W. Towner, S. B. Turkel & M. G . Wilson (1978). A fetus with recombinant of chromosome 8 inherited from her carrier father. Hum. Genet. 40, 241-248. Ishitobi, K., R. Harada, T. Ninomiya, Y. Santo & Y. Harada (1976). XEX translocation in a girl with gonadal dysgenesis. Yonago Acta rned. 20, 19-27. Kim, H. J., L. Y . F. Hsu & K. Hirschhorn (1974). Familial XEX translocation: t(X;X) (p22;q13). Cytogenet. Cell Genet. 13, 454464. Kristensen, H., U. Friedrich, G . Larsen & A. J. Therkelsen (1975). Structural X-chromosome abnormality in a female with gonadal dysgenesis. Hum. Genet. 26, 133-138. Laurent, C., M. C1. Biemont & B. Dutrillaux (1975). Sur quatre nouveaux cas de translocation du chromosome X chez l’homme. Hum. Genet. 26, 35-46. Paris Conference (1971). Standardization in human cytogenetics. Birth Defects: Original Article Series, Vol. VIII, No. 7.
lnvfx’-Bx recombinants
Fig. 8. Diagram showing process of pericentric inversion in X chromosome (a), and recombinant chromosomes resulting from a crossing over within the inversion loop (b).
abnormal X chromosome has two such centers, a proportion of t h e Barr bodies should be bipartite. In fibroblasts obtained from the proband, some of the cells analysed were found t o have bipartite Barr bodies. The present study provides further evidence in support of their hypothesis. It is well known that structurally abnormal X chromosomes invariably replicate late, f o r m X chromatin, and ar e inactive. These facts were well demonstrated in the observations of the recombinant X chromosome of the proband. Information concerning the replication pattern of the inverted human X chromosome is still limited. We have been able to find one case recorded in the literature of pericentric inversion of human X chromo-
266
MAEDA, OHNO, TAKADA, NISHIDA, TSUKIOKA AND TOMlTA
Quichaud, J . , J . de Grouchy, M. Vitse, I. Emerit & A. Dubreuil (1971). Syndrome de Turner 45,X/46,XXq+. Ann. Endocrinol. 31, 1153-1 155. Seabright, M. (1972). The use of proteolytic enzymes for the mapping of structural rearrangements in the chromosomes of man. Chromosoma (Berl.) 36, 204-210. Sumner, A. T. (1972). A simple technique for demonstrating centromeric heterochromatin. Exp. Cell Res. 75, 304-306.
Therman. E. & K. Patau (1974). Abnormal X chromosomes in man: Origin, behavior and effects. Hum. Genet. 25, 1-16. Address:
Tohru Maeda, M . D . Department of Laboratory Medicine Kitasato University School of Medicine 1, Asamizodai, Sagamihara, Kanagawa Japan
