Establishing A Clinical Screening System For External Genital Abnormalities Of DSD And Molecular Analysis Of AR With AIS

Background Disorders of sex development(DSD) is proposed, as defined by congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical,mostly caused by changes in genetic material. Before because the patient’s reproductive organs have characteristics of both sexes, this kind of disease is chronically named "hermaphroditism",and some scholars still use this name. According to its different causes, hermaphroditism is divided into the three categories: female pseudohermaphroditism, male pseudohermaphroditism and gonad dysplasia. However, hermaphroditism contains discriminatory meaning, causeing some negative impact on the patients and their family member’s psychology, living or working, and it has now been replaced by "DSD". The etiology of DSD is complex, having a variety of complicated clinical manifestations,and etiology diagnosis is relatively difficult,so until now the international classification is not unified. Until 2006, The Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology consider this kind of disease from a macro perspective, and puts forward suggestions,that DSD be divided into three categories: 46, XY DSD, 46,XX DSD and sex chromosome DSD.With the increasing awareness of the whole society for medical treatment, Disease detection rate of is significantly increased, but because of its complicated etiology and massive clinical manifestations, relativing to other diseases it’s is still low. The focus of each disease is being found early, early diagnosis and treatment, guiding prognosis and follow-up, therefore, improving the detection rate of DSD is an very important problem. Most of the patients with DSD see a doctor for various genital malformations,which are found at birth or soon,and that is better for early detection, early diagnosis and treatment than other clinical manifestations.At present, effective disease diagnosis and treatment processof DSD based external genital malformation is not established. Among them, the incidence rate of androgen insensitivity syndrome(AIS) included by 46, XY DSD is high,and its genetic background is complex, Containing the Y chromosome, germ cell tumor incidence rate and operation rate than other DSD is higher, From different degrees the patients fertility is affected, More importantly, It may leads to psychological abnormalities, abnormal behavior and cause irreparable loss to the society and family associated with abnormal sexual development. The gene diagnosis is the gold standard for the diagnosis of androgen insensitivity syndrome, and its pathogenic gene in recent years have been found, but because of its genetic background is complicated, needing to explore new pathogenic genes, It ’s beneficial to explain and establish the disease phenotype and gene type association, and provide basis of further gene diagnosis and prenatal diagnosis for patients and their families, to prevent of malignant tumor patient, to reduce or avoid the birth of the sick children prenatal diagnosis.Objective In this study, according to the different disease characteristics of genital malformations as the main clinical features with DSD, It‘s to establish a rapid screening process in order to achieve early detection, early diagnosis and treatment, guiding prognosis and follow-up. And, clinical tests and genetic diagnosis were performed in two pedigrees suspected to be with AIS.MethodsCollecting the case information of the patients with genital malformations as the main clinical features with DSD during the time of 2012 August to 2014 August in the First Affiliated Hospital of Zhengzhou University, including physical examination, endocrine indexes, imaging examinations, peripheral blood cell analysis of chromosome karyotype, and if necessary, laparoscopic exploration for gland excision or biopsy, and for individual patients external genital plastic surgery, establishing a clinical screening system for external genital abnormalities of DSD. Then we screen two androgen insensitivity syndrome family, besides that physical examination, karyotyping, endocrinal tests and color doppler ultrasound were performed in the probands and their female relatives.eight encoding exons of AR gene in patients suspected with AIS were amplified by PCR. The products were further analyzed by direct DNA sequencing.Results(1) Because external genital malformations is diverse, almost covering all disorders of sex development, and then screening the diseases with genital malformations as the main clinical features of DSD, conducive to the early diagnosis and treatment of DSD disease, and making harm for the family and society the minimum;(2) two androgen insensitivity probands caught AR gene mutations detected were c.2042T> C(I681T), c.1822C> T(R608X), family, female carriers detected in the heterozygous mutation of these sites. Pedigree a proband underwent laparoscopic gonadectomy surgery, confirmed gonads testicles.Conclusion(1) The establishment o of disease screening process for genital malformations as the main clinical features with DSD is better for early detection, early diagnosis and treatment of this disease;(2) c.2042T> C(I681T), c.1822C> T(R608X) is a two AIS family pathogenic mutations in patients, the AR gene genetic testing for 46, XY DSD, particularly insensitive to androgen syndrome effective diagnostic modality;(3) For all the patients with the abnormal development of the external genital organs, gene diagnosis is proposed as far as possible.