[Genetic analysis of genitourinary malformations].
OBJECTIVE
To analyze the expression of genes from chromosomal region 22q11.2 and assess the association between mutation(s) of particular gene(s) from this region and malformations of the urinary system.


METHODS
Expression of rat homologs of 33 genes from above region was determined in kidney tissues derived from rats of different fetal development ages (E13, E15, E19) and adulthood with reverse transcriptase-PCR. Potential mutation(s) in candidate gene SNAP29, whose expression pattern appeared to be unique, was screened in 44 patients and 220 normal controls with PCR-single strand conformation polymorphism (SSCP). Suspected positive regions were sequenced to verify the mutations.


RESULTS
Nine genes showed no expression throughout the whole development process; 18 genes with various expression levels showed continuous expression from the beginning of development; 6 genes only expressed for a short time, among which SNAP29 was selected for mutation screening. Upon sequencing, three mutations were identified from the 44 patients, including a G to A transition (GAG to AAG) in exon 2, and two A to G transitions (AGC to GGC) in exon 3.


CONCLUSIONS
Through systematic analysis of the expression of genes from chromosomal region 22q11.2, the SNAP29 gene was found to have a potential role in the development of genitourinary system. Two missense mutations were identified in three patients. These included one in exon 2 (featuring cryptorchidism), and the other in exon 3 (featuring cryptorchidism and hypospadia). Neither of the mutations was found in the normal controls. The results suggested that mutation(s) of gene(s) from chromosomal region 22q11.2 may play an important role in the genesis of genitourinary malformations.
Zhang
Jing-shu
JS
Sino-Dutch Biomedical and Information Engineering School, Northeastern University, Shenyang, Liaoning, People's Republic of China.
Fu
Yu
Y
Zhao
Yan-hui
YH
Li
Fei
F
Qian
Ai-li
AL
Wu
Bin
B
Li-Ling
Jesse
J
D000818:Animals; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D019038:Platelet Glycoprotein GPIb-IX Complex; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018807:Polymorphism, Single-Stranded Conformational; D050766:Qb-SNARE Proteins / Q000235:genetics*; D050767:Qc-SNARE Proteins / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000235:genetics*
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019038:Platelet Glycoprotein GPIb-IX Complex; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; C432420:SNAP29 protein, human; C094990:adhesion receptor