Isolated gonadotropin-releasing hormone (GnRH) deficiency, including Kallmann's syndrome (KS) and idiopathic hypogonadotropic hypogonadism (IHH), is a congenital disorder, which is characterized by a functional deficit in hypothalamic GnRH secretion. Despite recent advances in the understanding of the pathogenesis of the X-linked form of KS as the identification of the KAL gene (Xp22.3), the genetic basis of the sporadic form in female patients remains unclear. Although most searches for mutations in X chromosome have been reported in males, the newly recognized phenomenon of inheritance, such as genomic imprinting and uniparental disomy, raises the possibility of a female phenotype in the X- linked genetic defect. Here, the molecular study of the coding region of the KAL gene (exon 5 to 14) in 10 unrelated females with KS (n=6) or IHH (n=4) is reported. None of the subjects had familial histories of delayed puberty or hypogonadism. Samples from 4 healthy, unrelated female volunteers were used for identification of polymorphisms. PCR of the 10 exons of the KAL gene was performed on genomic DNA. The PCR products of the 10 exons were subject to single strand conformation polymorphism (SSCP) analysis to identify possible mutations. In an SSCP analysis of the amplified fragments (fragment size: 147 to 302 bp), no mutations or polymorphisms were found in any of the 10 patients and 4 controls. In conclusion, it is unlikely that KAL gene mutations are a clinically significant cause of sporadic GnRH deficiency in female patients, indicating the existence of defects in unidentified genes that result in the expression of the phenotypes in females.

Objective: To determine whether the LHβ-subunit gene missense mutation is present in Korean infertile patients with 46,XX POF, endometriosis and amenorrhea women. Design: Compare the electrophoretic band pattern of LHβ-subunit gene between infertile patients with 46,XX POF, endometriosis and amenorrhea patients and healthy nonpregnant women. Materials and Methods: Forty-five, 22 and 12 women were included in the study who presented to the infertility Medical Center at the CHA General Hospital and were diagnosed with POF, endometriosis and amenorrhea, respectively. 54 healthy nonpregnant women were used for control group. Samples of venous blood were collected from consenting individuals. DNA was extracted by standard methods. LHβ exon 2 was amplified with sequences derived from genomic DNA. Amplified DNA was digested by NcoI and FokI, agarose gel electrophoresis, ethidium bromide staining, and photography. Results: The variants of LHβ exon 2 (LHβ2) were studied in four different groups, such as POF, endometriosis, amenorrhea patients and nonpregnant women. The frequencies of LHβ exon 2 variants were slightly higher in POF patients (20.5%) than nonpregnant (16.7%) women. However, the variants in endometriosis and amenorrhea were not more frequent in the patients (18.2% and 16.7%) than in the nonpregnant (16.7%) women. The prevalence of POF, endometriosis and amenorrhea did not differ between patients with variant LH and normal LH. The infertile patients with the variant were not more frequent than healthy nonpregnant women with the variant. Conclusion: These mutations may not be specific in POF, endometriosis and amenorrhea patients, and further study is needed in healthy fertile (control) and POF women.