:: Asian Journal of Andrology ::

Karyotypic analysis of intersexuality in Chinese from Taiyuan

Zhen-Guo MI, Xiao-Feng YANG, Tao LAN

Department of Urology, First Affiliated Hospital, Shanxi Medical University, Taiyuan 030001, China

Asian J Androl 2000 Jun; 2: 155-157

Keywords: pseudohermaphroditism; hermaphroditism; karyotyping; gene; chromosome

Abstract

Aim: To analyze the kayrotypic patterns of 33 cases of intersexuality in Chinese from Taiyuan, China in order to further clarify its mechanism of development and the interrelationship between karyotype and phenotypic sex. Methods: High-resolution GTG-banding chromosome technique was used to analyze the karyotype patterns. Results: In these patients, 57.58% were male pseudohermaphrodites (46,XY), 18.18%, female pseudohermaphrodites (46,XX), 12.12%, true hemaphrodites, and 12.12%, other karyotypes. Although testes can be seen in 88.8% of karyotypes with Y chromosome, 73.68% of the patients were of female social sex. In 42.82% of patients the social sex is in conformity with their karyotypes. There were 2 cases of male pseudohermaphrodites, where the sex chromosome was normal, but abnormalities were found in chromosomes 9, 13, or 14. Conclusion: Sex chromosomes determine the direction of gonadal and sex differentiation, while the development of the normal gonad and external genitalia should have the participation of many autosomal chromosomes as well.

1 Introduction

Sex differentiation begins at the stage of zygote formation that dictates the chromosomal sex. Although the chromosomal sex is the key factor in the determination of phenotypic sex, many autosomes are also involved in sexual development^[1,2]. Gonadal differentiation into the testis or ovary is controlled by a multitude of genes, including the SRY, which is believed to be the testis-determining factor, as well as the SF-1, WT-1, DAX-1, and SOX9. The fully developed testis produces Mullerian inhibiting substance and testosterone, both of which are indispensable to the formation of the male phenotype, while the female phenotype develops in their absence. The molecular mechanism of the development of intersex is very complicated as both the sex chromosome and other factors are involved in the process of sex differentiation^[3]. The aim of the present study is to analyze the karyotypic patterns of intersex in Taiyuan in order to further clarify its mechanism of development and the interrelationship between karyrotype and phenotype sex.

2 Materials and methods

Thirty-three intersexual patients, 1.8-29.0 (mean 13.5) years of age, were recruited between 1985 and 1997. They were socially 11 males and 20 females, and only 2 were ambiguous; 18 cases were prepubertal subjects and 15 postpubertal. Their karyotypes were analyzed by the high-resolution GTG-banding chromosome technique^[1].

3 Results

The results are summarized in Table 1.

Table 1. Social, gonadal and chromosomal sex.

Case	Social sex	Testis	Ovary	Karyotype
1	F	+		XY
2	F			XY
3	F	+		XY
4	M	+		XY
5	F	+		XY
6	F	+		XY
7	F	+		XY
8	F	+		XY
9	F	+		XY
10	M	+		XY
11	F	+		XY
12	M	+		XY
13	F	+		XY
14	F			XY
15	M	+		XY
16	M	+		XY
17	F			XY
18	FM	+		XY
19	F	+		XY
20	F	+		XX
21	M	+		XX
22	F			XX
23	F			XX
24	F			XX
25	F			XX
26	M	+	+	XX/XYY
27	M	+	+	XX/XY
28	M	+		45,X/46,X,t(Y:Y)
29	FM	+		XX/XY
30	M	+		46,X,delY
31	M	+		47,XYY
32	F	+		XY,Inv9
33	F	+		XY,ter(13:14)

F=female; M=male; FM=ambiguous.

3.1 Karyotype classification

Nineteen cases (57.6%) were male pseudohermaphrodites (46,XY), 6 cases (18.2%) female pseudohermaphrodites (46,XX), 4 cases (12.1%) true hermaphrodites, and 4 cases (12.1%) other types of intersex. The karyotypes of the latter two categories were as follows: 1 case 46,XY,t(13:14)13qtercen14qter, 1 case 46,XY,Inv9,1 case 46,X,del(Y), 1 case 46,XXY, 2 cases 46,XY/46,XY, 1 case 46,XX/47,XYY, and 1case 45,X/46,X,t(Y:Y).

3.2 Chromosomal sex and social sex

In the 19 patients with 46,XY karyotype, there were 5 male social sex, 13 female social sex, and 1 ambiguous. In the 6 patients with 46,XX karyotype, there were 5 female and 1 male social sex. In the 8 patients with other karyotypes, there were 5 female social sex, 2 male social sex, and 1 ambiguous. It can be seen that in male pseudohermaphrodites there were 68.4% female social sex, while in female pseudohermaphrodites there were only 16.7% male social sex. In 6.0% prepuberty patients, it appeared difficult to determine their social sex. In 12/28 patients (42.9%), the social sex was in accordance with the sex chromosome.

3.3 Chromosomal sex and gonadal sex

In the 19 patients with 46,XY, 16 had palpable testicles, but in the 6 46,XX patients, only 2 had ovaries. Of the 4 true hermaphrodites, 2 cases had both testis and ovary, and the other 2 only testes. Abnormal testes were found in 88.8% of patients with Y chromosome.

3.4 Chromosomal sex and Autosome

In our study, there were 25 cases of normal karyotypes, six cases of abnormal chromosomal sex XX/XYY, XX/XY, 45,X/46,X,t(Y:Y), XX/XY, 46,X,delY, and 47,XYY, and 2 cases of abnormal autosome 46,XY,t(13:14) and 46,XY,Inv9.

4 Conclusions

Sex determination begins at fertilization and by week 5-7 of human embryonic development, the gonad is formed in accordance with the sex chromosome. A little later, the phenotypic sex and external genitalia are developed^[5]. Although the karyotype is the key element in sex determination, there are many other factors that influence the direction and course of sex differentiation. GTG-banding pattern analyzing technique has been used to diagnose human heredopathia, to study chromosomal structure, and to locate gene locus, as well as to analyze intersex karyotypes. In the present study, it was shown that the karyotypes were normal in twenty-five cases of intersex (Table 1), indicating that the sex chromosome was not the sole factor in the determinaton of sex. A hypothetical locus on the Y chromosome, termed the testis-determining factor, including the SRY and other related genes, is believed to be the switch that trigger on testicular development in XY individuals. However in our series of 27 cases with karyotypes containing Y chromosome, only 24 (88.9%) had testicle, and 15 (55.6%) presented female social sex. It suggests that besides the sex chromosome, other autosomal genes may also be involved in gonadal and sex differentiation. It has been shown that mutation of the 5-reductase gene at the number 2 chromosome^[3] and the and rogen receptor gene at Xq11-12.5^[4] may lead to pseudohermaphroditism; other autosomal genes related to sex development included the DAX-1, SOX9, SF-1, WT-1, 21-hydroxylase^[5-7], 17q^[8], and 10q25 and 9q22-24^[^9]. In our series, in 46,XY,Inv9 and 46,XY,t(13:14), although the sex chromosome was normal, they were pseudohermaphrodites. The authors believe that the sexual chromosome determines the direction of gonad differentiation, but many autosomal genes participated in normal gonad sex differentiation and development.

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Correspondence to: Dr Xiao-Feng YANG, Department of Urology, First Affiliated Hospital Shanxi Medical University, Taiyuan 030001, China
e-mail: urology@public.ty.sx.cn
Received 1999-10-08 Accepted 2000-04-17