Editor-in-Chief
Prof. Yi-Fei WANG,
Autosomal aberrations associated with testicular dysgenesis or spermatogenic arrest in Chinese patients
Jin-Hu GUO1, Pei-Yuan ZHU2, Yu-Feng HUANG2, Long YU1
1School of Life Sciences,
Institute of Genetics, Fudan University, Shanghai, 200433, China
2Laboratory of Reproduction & Genetics, Nanjing Jinling Hospital,
Nanjing 210002, China
Asian
J Androl 2002
Mar;
4: 3-7
Keywords:
autosomal aberration; testicular dysgenesis; male infertility; spermatogenic
arrest
Abstract
Aim: To analyze the relationship between autosomal aberrations and testicular dysgenesis or spermatogenic arrest in Chinese patients and to map the corresponding regions on each autosome in regard to the recorded aberrations accompanying these distubances. Methods: One hundred and nineteen cases of aberrant karyotypes with testicular dysgenesis, azoospermia or oligozoospermia reported in five Chinese journals and one monograph were analyzed. For each autosome, the type and frequency of chromosomal aberrations were counted and the regions corresponding to the disturbances were mapped out. Results: Chromosomes 13, 14, 9, 21 exhibited a high frequency of aberration and bands 14q11 and 13p11 were the two regions showing the highest linkage to testicular dysgenesis or infertility. The frequency of chromosomal aberrations was higher in bands 9p11 and 22q than in others. Conclusion: Conclusion: Autosomes 13, 14, 9 and 21 in the order of importance play a critical role in testicular development and spermatogenesis and other autosome may also contribute; the following regions, 14q11, 13p11,9p11, and 22q, are of high significance.1 Introduction
There is a close relationship between chromosome aberrations and testicular dysgenesis or spermatogenic arrest. Chromosomal aberration impairs the normal inactivation process of the X chromosome [1] or damages the structure of functional genes, which would lead to male infertility as a result of testicular dysgenesis or spermatogenic arrest.
Testicular development and spermatogenesis are very complicated processes and a large number of genes are involved. Many genes related to gonad development and spermatogenesis have been cloned and characterized, such as SRY, AZF, RBM, DAZ, USP9Y, TSPY, DFFRY, CREM, MIS, UTY, etc., most of which are located on the male-specific Y chromosome. However, some of them are located on the autosomes, such as WT1 on 11, SOX9 on 17, DAZLA on 3 and FSHR on 2 [2,3]. Y chromosome is the smallest one in human and only a few genes have been found therein. Genes on the Y chromosome have been studied in detail and methods have been developed to diagnose the defects of DAZ and other genes [4-6]. However, genes on the autosomes have not been investigated systematically. Hence, study on the correlation between autosomal aberrations and relevant disturbances is helpful for cloning functional genes related to gonad, testis development and spermatogenesis, and for revealing the mechanisms of these processes both at the chromosome and the gene levels. The present review analyzed 119 cases of aberrant karyotypes with testicular dysgenesis, azoospermia or oligozoospermia reported in Chinese literature in order to help clarifying the relationship between autosomal aberrations and these disturbances.
2 Materials and methods
Articles related to male reproductive defect with aberrant karyotypes published in the Chinese Journal of Medical Genetics (from 1990 to 2000), the Chinese Journal of Birth Health & Heredity (1993 to 2000), the National Medical Journal of China (1977 to 1999), the Chinese Medical Journal (1980 to 1999), the Journal of Improving Birth Outcome and Child Development of China (1994 to 1999), and the Chromosomal atlas of the first reported aberrant karyotypes in the world among Chinese ( Xia JH, Li LY, Ed., Zhengzhou, Henan Science And Technology Publishing House, 1993) were collected. Patients quoted in these literatures were from various parts of China, including Beijing, Tianjin, Xinjiang, Guangdong, Hebei, Fujian, Hunan, Jiangsu, Chongqing, Sichuan, Liaoning, Gansu and Shandong. Some karyotypes were reported the first time in the world. Chromosomal aberrations in these cases included deletion, inversion, insertion, translocation, etc. The clinical manifestations were also manifold, such as cryptorchidism, testicular dysgenesis, malformed sperm, low motility sperm, oligozoospermia, azoospermia and infertility of unidentified cause. In 63 cases (Table 1) the aberrant autosome regions were described in detail so that they could be employed to construct the autosome regional map, reflecting the correlation between the chromosomal regions and the disturbances. In the remaining 56 cases, although the aberrant chromosomes were indicated, the regions were not. In the 119 patients, the frequency of aberrations in each autosome was analyzed in cases showing identical karyotypes. As indicated above, 63 cases were employed to construct the regional map.
Table 1. Sixty-three cases employed in constructing the map of "hot" regions on autosomes.
|
Karyotype |
Number
of cases |
Disturbance |
Reference |
|
46,XY,t(2;7)(p21;q11) |
1 |
Testicular
dysgenesis |
8 |
|
46,XY,t(7;8)(p11;q21) |
1 |
Testicular
dysgenesis |
8 |
|
46,XY,t(13;16)(q14;q22) |
1 |
Infertility |
11 |
|
46,XY,inv(9)(p11;p12) |
2 |
Infertility |
11 |
|
46,XY,inv(9)(p11;q13) |
3 |
Infertility |
11 |
|
45,XY,t(13;14)(p11;q11) |
2 |
Infertility |
11 |
|
45,XY,t(14;21)(p11;q11) |
1 |
Infertility |
11 |
|
45,XY,t(13;15)(q11;p11) |
1 |
Infertility |
15 |
|
45,XY,t(15;21)(p11;q11) |
1 |
Infertility |
15 |
|
45,XY,t(13;14)(p11;q11) |
2 |
Infertility |
15 |
|
46,XY,t(1;8)(p22;q21) |
1 |
Infertility |
15 |
|
46,XY,inv(5)(p13;q15) |
1 |
Infertility |
15 |
|
46,XY,t(1;14)(p11;q11) |
1 |
Infertility |
15 |
|
46,XY,t(5;22)(q35;q11) |
1 |
Infertility |
15 |
|
46,XY,inv(9)(p11;q21) |
1 |
Infertility |
15 |
|
46,XY,t(6;9)(q21;p24) |
1 |
Infertility |
15 |
|
45,XY,t(14;15)(p11;q11) |
1 |
Infertility |
15 |
|
45,XY,t(5;22)(5p->5q15::22q11->22qter) |
1 |
Low
sperm motility |
16 |
|
46,XY,inv(1),t(1;6)(1qter->1q25::1p13->1q25::1p13->1p22::6q23->6qter;6pter->6q23::1p22->1pter) |
|||
|
|
1 |
Azoospermia |
17 |
|
45,XY,rob(13;14)(p11;q11) |
8 |
Infertility |
18 |
|
45,XY,rob(14;15)(p11;q11) |
1 |
Infertility |
18 |
|
45,XY,rob(14;21)(p11;q11) |
1 |
Infertility |
18 |
|
45,XY,rob(21;22)(p11;q11) |
1 |
Infertility |
18 |
|
46,XY,t(1;4)(p21;q35) |
1 |
Infertility |
18 |
|
46,XY,t(2;3)(q23;q27) |
1 |
Infertility |
18 |
|
46,XY,t(2;18)(p13;q21) |
1 |
Infertility |
18 |
|
46,XY,t(3;13)(q27;q21) |
1 |
Infertility |
18 |
|
46,XY,t(4;13)(q35;q22) |
1 |
Infertility |
18 |
|
46,XY,inv(1)(p36;q21) |
1 |
Infertility |
18 |
|
47,XY,inv(3)(p21;q21) |
1 |
Infertility |
18 |
|
46,XY,t(14:20)(14pter->14q11::20q13->20qter,20pter->20q13::14q11->14qter) |
|||
|
|
1 |
Azoospermia |
20 |
|
46,XY,t(1;4)(p31;q35) |
1 |
Cryptorchidism |
22 |
|
46,XY,t(1;7)(p32;q35),inv(12)(q15q24) |
1 |
Cryptorchidism |
22 |
|
46,XY,t(1;11)(p36;q13) |
1 |
Azoospermia |
22 |
|
46,XY,inv(2)(p11q31) |
1 |
Teratospermia |
22 |
|
46,XY,t(6;13)(p25;q12) |
1 |
Azoospermia |
22 |
|
46,XY,del(7)(q11q22) |
1 |
Microphallus
& cryptorchidism |
22 |
|
46,XY,inv(10)(q11q22) |
1 |
Oligozospermia |
22 |
|
45,XY,ter
rea(14;22)(q32.2;p13) |
1 |
Testicular
dysgenesis |
22 |
|
46,XY,del(19)(q12) |
1 |
Azoospermia |
22 |
|
46,XY,t(6;7)(6pter->6p21;
7qter->7p22::6p21->6pter) |
|||
|
|
1 |
Azoospermia |
23 |
|
46,XY,t(6;10)(6pter->6q22;10qter->10p15::6q22->6qter) |
|||
|
|
1 |
Azoospermia |
23 |
|
46,XY,del(6)(6qter->6p12) |
1 |
Azoospermia |
23 |
|
46,XY,inv(9)(p21->p24::p13::q21->qter) |
1 |
Azoospermia |
23 |
|
46,XY,t(8;13)(8qter->8p12::13q12->13qter);del(8)(p12->pter);del(13)(pter->q12) |
|||
|
|
1 |
Azoospermia |
23 |
|
46,XY,t(4;11)(4pter->4q31::11q23->11qter;11pter->11q23::4q31->4qter) |
|||
|
|
1 |
Azoospermia |
25 |
|
46,XY,t(6;9)(q13;p24)pat |
1 |
Teratospermia |
27 |
|
46,XY,del(22)(q13->qter) |
4 |
Azoospermia |
27 |
3
Results
From Figure 1, it can be seen that in Chinese patients aberrations leading to testicular dysgenesis, spermatogenic arrest and infertility were distributed almost over all the autosomes, with chromosome 13, followed by 14 showing the highest incidence. Chromosomes 9, 21, 22, and 1, in the order of incidence also displayed a high occurrence of aberrations, while chromosomes 2, 3, 4, 5, 6, 7, 8, 10, 11, 12, 15, 16, 17, 18, 19 and 20 had relatively low aberration rates (Fugire 1).
Figure 1. Number of aberration cases on each autosome.
Figure 2 shows the "hot" regions on the 22 autosomes. Aberrations in these regions could result in testicular dysgenesis, oligozoospermia, azoospermia or male infertility of unidentified cause. Small rectangles at the side of the regions indicated the number of cases showing the particular aberration. Bands 14q11 and 13p11 were the two regions ex