HOXA13 Gene Analysis In Patients With Mǖllerian Duct Abnormalities

BACKGROUNDS This article aims to study the relationship between the polyalanine tracts expansion or polymorphism in exon 1 and point mutation in exon 2 of H0XA13 gene and Mullerian duct abnormalities. HOXA13 gene belongs to HOX (homobox) genes which encode a highly conserved family of transcription factors, which play a fundamental role in embryonic morphogenesis. In humans there are 39 HOX genes organized into four clusters named HOXA through HOXD, each cluster is located on a different chromosome, and contains 9-11 genes. The order of the genes within each cluster corresponds closely to their temporal and spatial expression patterns during development: genes at the 3' end of each cluster are expressed early, in anterior and proximal regions, whereas genes at the 5' end of each cluster are expressed later, in posterior and distal regions. HOX proteins help pattern the developing embryo along both the primary (rostro-caudal) and secondary (limb and genital bud) body axes. They therefore play an important role in the development of the central nervous system, axial skeleton, gut and urogenital tract, as well as the limbs and external genitalia. Mullerian duct abnormalities have higher similarity in phenotype with hand-foot-genital syndrome. Hand-foot-genital syndrome (HFGS [MIM 140000]) is a rare, dominantly inherited condition characterized by distal limb and distal genitourinary tract malformations. These limb abnormalities are fully penetrant, bilateral, and symmetrical, with little variation in severity. By contrast, the urogenital tract malformations show incomplete penetrance and variable severity. Genital abnormalities include hypospadias in males and Mullerian duct fusion defects in females .The latter range from isolated longitudinal vaginal septum to double uterus with double cervix, which can lead to miscarriage, premature labor, and stillbirth. The mutations in HOXA13 gene discovered in HFGS so far fall into three classes: truncation mutations, polyalanine tract expansions and an amino acid substitution in the homeodomain. But the genetic etiology of Mullerian duct abnormalities is still unknown, few domestic research had been seen.OBJECTIVES To investigate whether or not HOXA13 gene mutation existed in Chinese patients with Mullerian duct abnormalities as well as associativity analyzing.METHODS According to abroad literatures reported polyalanine tracts expansion in exon 1 and point mutation in exon 2 of HOXA13 gene were found in patients with HFGS, HOXA13 gene was detected in 58 Chinese patients (including 42 patients with incomplete Mullerian fusion, 16 patients with Mullerian aplasia) and 54 control individuals. PCR amplificated the objective fragments, capillary electrophoresis analyzed the polyalanine tracts of exon 1 and the homeodomain of exon 2 was sequenced in the identical patients and controls.RESULTS The result of capillary electrophoresis analysis of exon 1 in HOXA13 gene displays uniform PCR productive peak around 430base in all patients and controls which hints no length changes or polymorphism of polyalanine tracts were found. Directed automatic sequencing of exon 2 in H0XA13 gene reveals that no mutations were found in patients and controls.CONCLUSIONS Length expansion of polyalanine tracts and homeodomain mutation of HOXA13 gene may not be the correlated etiological factors which lead to Mullerian duct abnormalities in Chinese patients. We need more studies to elucidate the etiology of Mullerian duct abnormalities in Chinese individuals.