Analysis of homeobox gene HOXA10 mutations in cryptorchidism

被引:56
作者
Kolon, TF [1 ]
Wiener, JS [1 ]
Lewitton, M [1 ]
Roth, DR [1 ]
Gonzales, ET [1 ]
Lamb, DJ [1 ]
机构
[1] Texas Childrens Hosp, Baylor Coll Med, Scott Dept Urol, Dept Cell Biol, Houston, TX 77030 USA
关键词
cryptorchidism; mutation; genes; homeobox; testes; molecular biology;
D O I
10.1016/S0022-5347(01)62132-3
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: Cryptorchidism is the most common congenital abnormality of the genitalia. However, its exact etiology remains to be defined. Homeobox (HOX) containing genes have a key role in the morphogenesis of segmental structures along the primary body axis, including the urogenital mesenchyma. In male mice with a targeted deletion of the HOXA10 gene cryptorchidism manifests in the absence of other major defects. Because to our knowledge this gene has never been examined for alterations in humans, we evaluated whether mutations of HOXA10 are associated with cryptorchidism in humans. Materials and Methods: Genomic deoxyribonucleic acid (DNA) was extracted from human blood or tissue samples from 16 noncryptorchid control subjects and 45 cryptorchid boys. To screen for mutations exons 1 and 2 of the HOXA10 gene were amplified individually by polymerase chain reaction using 6 overlapping oligonucleotide primer pairs. Single strand conformational polymorphism (SSCP) analysis of the amplified radiolabeled DNA fragments was performed. Variant band shifts were detected due to abnormal migration of the denatured DNA fragment compared to controls, suggesting an alteration in the DNA sequence. Sequence analysis of these variant bands was then done to define any mutations. Results: SSCP analysis revealed variants in 2 controls. Of the 45 samples from cryptorchid patients 30 had SSCP variants in exon 1. No variants were found in other regions of the gene. Sequence analysis revealed several DNA polymorphisms in exon 1 in controls and boys with cryptorchidism. Other nucleotide changes (point mutations) were noted only in exon 1 in the DNA of 5 cryptorchid patients, of whom 1 had a 24 nucleotide deletion. Conclusions: Our initial analysis of the HOXA10 gene in humans demonstrates that genetic alterations of this gene may be present in some boys with cryptorchidism. HOXA10 polymorphisms exist in normal control subjects as well as in cryptorchid patients. Further analysis of the function of the mutated protein will elucidate the role of this gene as a potential causative factor of testicular descent.
引用
收藏
页码:275 / 280
页数:6
相关论文
共 14 条
[1]  
BENSON GV, 1995, MOL CELL BIOL, V15, P1591
[2]  
Benson GV, 1996, DEVELOPMENT, V122, P2687
[3]   Control of morphogenesis and differentiation by HOM/Hox genes [J].
Botas, Juan .
CURRENT OPINION IN CELL BIOLOGY, 1993, 5 (06) :1015-1022
[4]   THE LENGTH AND LOCATION OF CAG TRINUCLEOTIDE REPEATS IN THE ANDROGEN RECEPTOR N-TERMINAL DOMAIN AFFECT TRANSACTIVATION FUNCTION [J].
CHAMBERLAIN, NL ;
DRIVER, ED ;
MIESFELD, RL .
NUCLEIC ACIDS RESEARCH, 1994, 22 (15) :3181-3186
[5]   THE STRUCTURAL AND FUNCTIONAL-ORGANIZATION OF THE MURINE HOX GENE FAMILY RESEMBLES THAT OF DROSOPHILA HOMEOTIC GENES [J].
DUBOULE, D ;
DOLLE, P .
EMBO JOURNAL, 1989, 8 (05) :1497-1505
[6]   Patterning in the vertebrate limb [J].
Duboule, Denis .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 1991, 1 (02) :211-216
[7]   GENETIC-VARIATION AT 5 TRIMERIC AND TETRAMERIC TANDEM REPEAT LOCI IN 4 HUMAN-POPULATION GROUPS [J].
EDWARDS, A ;
HAMMOND, HA ;
JIN, L ;
CASKEY, CT ;
CHAKRABORTY, R .
GENOMICS, 1992, 12 (02) :241-253
[8]  
Hayashi K, 1991, PCR Methods Appl, V1, P34
[9]   STRONG CORRELATION BETWEEN THE NUMBER OF CAG REPEATS IN ANDROGEN RECEPTOR GENES AND THE CLINICAL ONSET OF FEATURES OF SPINAL AND BULBAR MUSCULAR-ATROPHY [J].
IGARASHI, S ;
TANNO, Y ;
ONODERA, O ;
YAMAZAKI, M ;
SATO, S ;
ISHIKAWA, A ;
MIYATANI, N ;
NAGASHIMA, M ;
ISHIKAWA, Y ;
SAHASHI, K ;
IBI, T ;
MIYATAKE, T ;
TSUJI, S .
NEUROLOGY, 1992, 42 (12) :2300-2302
[10]   EVOLUTION OF THE VERTEBRATE HOX HOMEOBOX GENES [J].
KRUMLAUF, R .
BIOESSAYS, 1992, 14 (04) :245-252