Clinical And Genetics Analysis Of Hypergonadotropic Hypogonadism

Objective: To study the genetic pathogenesis of hypergonadotropic hypogonadism(HH).Method:1.Clinical study: the medical history of two female patients with HH were collected.Clinical inspection including pelvic ultrasound,sex hormone levels,karyotype,liver function,renal function,glucose and lipid metabolism were done.2.Genetic research2.1 5ml peripheral blood was collected from 2 patients and normal samples,the genomic DNA was extracted by DNA extraction kit.2.2 Affymetrix CytoScan HD array was applied to detected and analysis the chromosome structure changes of 2 HH female patients from a inbreeding familyResult:1.Clinical research: The first patient: FT3/FT4/TSH were normal,cortisol at 8 o'clock and ACTH were normal,the concentration of FSH/LH/PRL/E2 were 78.76 IU/L,23.19 IU/L,312.29 m IU/L,40.0 pmol/L.And 2.36 nmol/L,0.17 nmol/L of progesterone/testosterone.The concentration of Beta-HCG was 1.54 IU/L and GH was 0.149ug/L,the karyotype was 46 XX,the liver function,renal function,blood glucose and blood lipid,blood electrolyte were also normal,and the blood cell number was also normal.The pelvic ultrasound showed a primordial uterus size with 16 ×15 ×10 mm3 and a unilateral endometrial thickness with 1 mm.Bilateral ovaries was not detected,the inguinal region showed no obvious or abnormal mass,there was no obvious abnormal in bladder.The second patient: FT3/FT4/TSH were normal,cortisol at 8 o'clock and ACTH were normal,the concentration of FSH/LH/PRL/E2 were 64.18 IU/L,24.38 IU/L,131.55 m IU/L,161.0pmol/L.And 1.47 nmol/L,0.55 nmol/L of progesterone/testosterone.Beta-HCG and GH were normal,the karyotype was 46 XX,the liver function,renal function,blood glucose and blood lipid,blood electrolyte were also normal,while the blood cell number was higher.The pelvic ultrasound showed a primordial uterus size with 13 ×12 ×10 mm3.Bilateral ovaries was not detected,the inguinal region showed no obvious or abnormal mass,there was no obvious abnormal in bladder.2.Cytogenetics research: Affymetrix Cyto Scan HD chromosome chip was used to detect the chromosome linkage status and the structural changes of chromosome.The copy number variation was not found in 2 patients.But,we found LOH in chromosome 2,5 and chromosome 22 in first patient,the fragment size was 28.3Mb,16.8Mb and 14.5Mb respectively.Second patients had partial LOH in chromosome 1,2 and chromosome 5,and the fragment sizes were 19 Mb,37.3Mb and 15.3Mb respectively.The LOH fragments of two patients in chromosome 2(2q.21—2q22.2)and 5(5q21.3—5q23.2)were overlapped which included genes RAB3GAP1 /ZRANB3 /LCT /THSD7 B /SNORA72.Among these genes,RAB3GAP1 may be associated with hypogonadism of patients.Conclusion: The etiology of these two patients with HH may be linked to microdeletion in chromosome 2 or chromosome 5.