Klinefelter syndrome with partial androgen insensitivity syndrome: a case report and literature review / 中华实用儿科临床杂志

The clinical data of a patient with Klinefelter syndrome (KS) complicated by partial androgen insensitivity syndrome (PAIS) was retrospectively analyzed.The patient, a 2-month-and-22-day-old baby, was admitted to Children′s Hospital Affiliated to Zhengzhou University due to abnormal external genitalia in October 2021.Upon birth, the patient exhibited abnormal external genitalia, manifested as clitoral hypertrophy.Hormonal examinations were consistent with those of peers, while chromosomal analysis revealed 47, XXY.Due to the severe undermasculinization, whole exome sequencing was conducted, indicating a heterozygous variant of the AR gene (c.1847G>A, p.Arg616His). The patient was diagnosed with PAIS, and her elder sister was diagnosed with complete androgen insensitivity syndrome.For further treatment, a multidisciplinary comprehensive evaluation is needed.This is a rare case of KS combined with PAIS, suggesting the possibility of AR gene mutations in KS children with severe undermasculinization.

Three cases of partial androgen insensitivity syndrome and literature review / 中国基层医药

Objective:To investigate the clinical features, diagnosis, treatment, and future sex selection in patients with partial androgen insensitivity syndrome (PAIS).Methods:Retrospective analysis of clinical data of three patients with PAIS who received treatment in The Third Affiliated Hospital of Xi'an Medical University, Beijing Ditan Hospital of Capital Medical University, and Beijing Yayuncun Amcare Women's and Children's Hospital from 2013 to 2015 was conducted. Physical signs, specialized examinations, surgical explorations, and treatments were analyzed. The Chinese database was searched, and 12 cases of PAIS were collected and summarized.Results:Fifteen patients with PAIS presented with primary amenorrhea (15/15). Special clinical manifestations included gender as male or appearing as male (5/15), penile dysplasia or clitoral hypertrophy (14/15), urethral dysplasia (5/15), and breast development (4/15). Eleven cases were treated based on female gender (including surgery and hormone replacement therapy). There were three special patients with PAIS who had specific etiology, genetics, clinical manifestations, histopathology, diagnosis, and treatment and ultimately underwent treatment based on female gender.Conclusion:PAIS is a rare form of disorder of sex development, featuring a karyotype of 46, XY, and is a congenital X-linked recessive condition. Understanding the pathogenesis of PAIS more thoroughly can contribute to accurate diagnosis, personalized treatment, and well-organized follow-up, thereby preventing gender dysphoria.

Androgen Insensitivity Syndrome: A Case Report

Background: Androgen insensitivity syndrome refers to an inability of the body to respond properly to male sex hormones (androgens) produced during pregnancy. This occurs because of a change (mutation) in a gene involved in the production of the protein inside cells that receives the androgen hormone and instructs the cells in how to use it. This is a genetic disorder that makes XY foetuses insensitive (unresponsive) to androgens, they are born looking externally like normal girls and Internally, there is a short blind pouch vagina and no uterus, fallopian tube or ovaries. There are testes in the abdomen or in the inguinal canal. The CAIS is usually detected at puberty when a girl should but does not begin to menstruate. They are at high risk of osteoporosis so should take oestrogen replacement therapy. Case Report: PAIS results in micropenis with hypospadias and gynaecomastia. We report this rare case of 18yr old female patient with primary amenorrhea. Subsequent investigation including karyotyping revealed that the patient is phenotypically female but genotypically male with testes. Gonadectomy was done with proper counselling and patient was put on hormonal replacement replacement therapy.

Complete Androgen Insensitivity Syndrome: Diagnosis and Psychological Impact in Two Adolescents, A Case Report

@#This case report illustrates two cases of complete androgen insensitivity syndrome (CAIS) which is a rare form of sexual development disorder. Both presented with primary amenorrhea at the age of 18 and 19 years old. The hormonal profiles ruled out hypothyroidism, hyperprolactinemia, and primary ovarian failure. Magnetic resonance imaging of both patients showed the absence of uterus, fallopian tubes, ovaries, but the presence of proximal 1/3rd of the vagina. There is a single testis in the left inguinal region with unknown status of spermatogenesis. Women with CAIS are vulnerable to various psychological conditions caused by the appalling fact of being genotypically male when they have been raised female all their life. The gender confusion, reproductive issues, and how others perceive them require sensitive support. Hence, accentuate the need to explore and address the emotional, psychological, and psychiatric vulnerabilities, religious and spiritual beliefs in issues of relationships, infertility, and conception.

Androgen Insensitivity Syndrome with Bilateral Cryptorchidism and Seminoma in Tibet:Report of One Case / 中国医学科学院学报

Androgen insensitivity syndrome(AIS)with bilateral testicular malignant transformation is very rare,and its diagnosis should be based on clinical manifestations,physical examination,serological findings,karyotype analysis,and pathological findings.This study reported a case of complete androgen insensitivity syndrome among Tibetan in Tibet.It took 17 years from the discovery of congenital absence of uterus to bilateral pelvic mass resection.Pathological examination confirmed that bilateral pelvic space occupying lesions were dysplastic testicular tissue with seminoma and sertoli cell adenoma-like nodules.This study summarized the clinicopathological features to deepen the understanding of the disease.

Atendendo mulheres com cariótipo 46, XY / Attending women with 46, XY karyotype

As diferenças ou distúrbios do desenvolvimento sexual (DDS) compreendem um grupo heterogêneo de condições congênitas que resultam na discordância entre os cromossomos sexuais, as gônadas e/ou o sexo anatômico de um indivíduo. A classificação desses distúrbios é baseada no cariótipo conforme o Consenso de Chicago de 2006 e substitui os termos pseudo-hermafroditismo, hermafroditismo e intersexo. O objetivo desta revisão é fornecer ao ginecologista conhecimentos básicos sobre a etiologia, fisiopatologia e orientações das principais anormalidades de DDS para uma avaliação diagnóstica e terapêutica no atendimento de mulheres na infância, adolescência e em idade adulta com cariótipo 46,XY. O diagnóstico deve ser realizado pela interação entre o exame clínico as dosagens hormonais, os exames de imagem e a análise genética, desde o cariótipo até o estudo de alterações dos genes por técnicas de biologia molecular. O tratamento é realizado de acordo com a etiologia e inclui intervenções cirúrgicas como a gonadectomia e plásticas sobre a genitália externa, terapia de reposição hormonal e apoio psicológico. São necessárias a individualização dos casos e uma equipe interdisciplinar, para um atendimento adequado às mulheres com cariótipo 46,XY.(AU)

Differences or disorders of sexual development (DSDs) comprise a heterogeneous group of congenital conditions that result in the disagreement between an individual's sex chromosomes, gonads and/or anatomic sex. The classification of these disorders is based on the karyotype according to the 2006 Chicago Consensus and replaces the terms pseudohermaphroditism, hermaphroditism and intersex. The aim of this review is to provide the gynecologist with basic knowledge about the etiology, pathophysiology and guidelines of the main abnormalities of DDS for a diagnostic and therapeutic evaluation in the care of women in childhood, adolescence and adulthood with a karyotype 46,XY. The diagnosis must be made by the interaction between clinical examination hormonal measurements, imaging and genetic analysis from the karyotype to the study of gene alterations by molecular biology techniques. Treatment is carried out according to the etiology and includes surgical interventions such as gonadectomy and plastic surgery on the external genitalia, hormone replacement therapy and psychological support. Individualization of cases and an interdisciplinary team are required to provide adequate care for women 46,XY karyotype.(AU)

Complete Androgen Insensitivity Syndrome: A Rare Case of Prenatal Diagnosis / Síndrome de insensibilidade completa aos androgênios: um caso raro de diagnóstico pré-natal

Abstract With the widespread uptake of noninvasive prenatal testing (NIPT), a larger cohort of women has access to fetal chromosomal sex, which increases the potential to identify prenatal sex discordance. The prenatal diagnosis of androgen insensitivity syndrome (AIS) is an incidental and rare finding. We wish to present the diagnosis of a prenatal index case after NIPT of cell-free fetal DNA and mismatch between fetal sex and ultrasound phenotype. In this particular case, the molecular analysis of the androgen receptor (AR) gene showed the presence of a pathogenic mutation, not previously reported, consistent with complete androgen insensitivity syndrome. Carrier testing for the mother revealed the presence of the same variant, confirming maternal hemizygous inheritance. Identification of the molecular basis of these genetic conditions enables the preimplantation or prenatal diagnosis in future pregnancies.

Resumo Com a utilização generalizada de testes pré-natais não invasivos (TPNIs), uma crescente porção de mulheres tem acesso ao sexo cromossômico fetal, o que aumenta o potencial para identificar discordância sexual pré-natal. O diagnóstico pré-natal da síndrome de insensibilidade androgénica é um achado incidental e raro. Pretendemos apresentar um caso índice de diagnóstico pré-natal por meio de DNA fetal livre e incompatibilidade entre sexo fetal e fenótipo ecográfico. Neste caso particular, a análise molecular do gene do receptor de andrógenios (RA) revelou a presença de uma mutação patogênica, não relatada anteriormente, consistente com a síndrome de insensibilidade completa aos androgênios. A mãe revelou ser portadora da mesma variante, confirmando a hereditariedade hemizigótica. A identificação da base genética permite o diagnóstico pré-implantação ou pré-natal em futuras gestações.

Síndrome de insensibilidad a andrógenos: revisión bibliográfica a propósito de 5 casos / Androgen insensitivity syndrome: literature review about 5 cases

El síndrome de insensibilidad a andrógenos (AIS en la sigla inglesa) es una entidad muy poco frecuente en endocrinología. Se caracteriza por la mutación del receptor de andrógenos de magnitud variable, por medio del cual individuos 46,XY no se virilizan normalmente, a pesar de conservar sus testículos y tener concentraciones de testosterona en rango masculino. El cuadro clínico es variable y depende la profundidad de la alteración del receptor. En un extremo, hay casos de insensibilidad androgénica completa (CAIS) con fenotipo femenino. En el otro extremo hay insensibilidad parcial (PAIS) que se extiende desde el fenotipo femenino, con o sin ambigüedad genital, hasta los casos de hombres infértiles o con subvirilización, que presentan insensibilidad androgénica más leve. En los fenotipos femeninos, los testículos suelen estar en posición ectópica y aquellos ubicados dentro del abdomen tienen riesgo de malignizarse, por lo que suelen extirparse. Estos son los casos de más difícil manejo, pues aparte de la necesidad de gonadectomía seguida de terapia hormonal femenina, existe una vagina estrecha y en fondo de saco ciego y que suele requerir corrección quirúrgica para permitir la actividad sexual. En este trabajo presentamos 5 casos de AIS vistos recientemente en 2 centros clínicos de Santiago y que ilustran la heterogeneidad de presentación. Además, hacemos una revisión actualizada de los criterios diagnósticos, los tratamientos más adecuados y el manejo global de esta condición.

The Androgen insensitivity syndrome (AIS, in its English acronym) is a very rare entity in endocrinology. It is characterized by a variable magnitude androgen receptor mutation, whereby 46, XY individuals are not normally virilized, despite retaining their testicles and having testosterone concentrations in the male range. The clinical picture is variable and depends on the depth of the receptor alteration. At one extreme, there are cases of complete androgenic insensitivity (CAIS) with a female phenotype. At the other extreme, there is partial insensitivity (PAIS) that extends from the female phenotype, with or without genital ambiguity, to cases of infertile or undervirilized men, who have milder androgenic insensitivity. In female phenotypes, the testes are usually in an ectopic position and those located within the abdomen are at risk of malignancy, and therefore are usually removed. These are the most difficult cases to manage because apart from the need for gonadectomy followed by female hormonal therapy, there is a narrow vagina and a deep blind pouch that usually requires surgical correction to allow sexual activity. In this work, we present 5 cases of AIS recently seen in 2 clinical centers in Santiago and that illustrate the heterogeneity of presentation. In addition, we make an updated review of the diagnostic criteria, the most appropriate treatments, and the overall management of this condition.

Complete androgenin sensitivity syndrome presenting with primary amenorrhoea and inguinal mass: a case report

Androgen insensitivity syndrome (AIS), also known as testicular feminization, an X-linked recessive disorder comprises a wide range of phenotypes that are caused by various types of mutations in the androgen receptor gene. AIs can be classified as complete, partial, or mild based on the phenotypic presentation. The clinical findings include a female type of external genitalia, 46-XY karyotype, absence of Mullerian structures, presence of Wolffian structures to various degree, and normal to high testosterone and gonadotropin levels. We report this case as an interesting and rare syndrome. The patient is a 15-year-old phenotypic female who presented with primary amenorrhea and normal-appearing external genitalia. Orchidectomy was done after proper counselling and proper psychological support was given to her.

Histopathological spectrum of disorders of sexual development: a case series of seven cases

Disorders of sexual development (DSD) refer to cases in which there is a discordance among at least two of the following; genetic sex, gonadal sex, genital tract sex and phenotypic sex. DSDs are quite rare with reported incidence varying from 1 in 4,500 to 1 in 5,500. Ovotesticular disorder is amongst the rarest variety of DSD comprising only to 3-10% of all cases of DSD with only 500 cases reported till now worldwide. Frequency of MRKH syndrome is 1 in 4,500 cases and is the cause of amenorrhoea in 15% of cases of primary amenorrhoea. Authors present a case series of seven cases of DSDs with three cases diagnosed as androgen insensitivity syndrome, two cases of true ovotesticular DSD (true hermaphrodite), one case each of mixed gonadal dysgenesis and Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome. Authors received the histopathology specimen of these cases in this department which was extensively sampled to study the gonads and the other derivatives of Mullerian and Wolffian duct and to rule out presence of any malignancy.

Síndrome de insensibilidad androgénica. A propósito de un caso clínico / Androgenic insensitivity syndrome. About a clinical case

RESUMEN El síndrome de insensibilidad androgénica (SIA) es una de las anormalidades de la diferenciación sexual (desarrollo sexual diferente). Es un trastorno genético dependiente del cromosoma X, produce una alteración en el receptor de andrógenos, se asocia con testículos en las mujeres cuyo cariotipo es XY y con agenesia vaginal y uterina. Acuden a la consulta médica los padres con su hija recién nacida de 12 días de edad. Motivo de consulta: masa en la región inguinal derecha. Examen físico: signos vitales normales, activa al manejo, reactiva. Se observa una masa en la región inguinal derecha de aproximadamente 2 cm de diámetro, reductible, no dolorosa. Genitales externos femeninos: normales. La paciente es referida al Servicio de Cirugía para proceder a la corrección del defecto herniario. Se indica realizar un estudio citogenético y medir los niveles hormonales en sangre. Resultado del estudio anatomopatológico posquirúrgico, luego de 7 días de haber sido intervenida quirúrgicamente: "Tejido gonadal de tipo testicular con zonas de congestión vascular y hemorragia focal". Los niveles hormonales sanguíneos son normales; el cariotipo es normal masculino XY. Diagnóstico: debido a que el resultado del cariotipo es concluyente, se diagnostica síndrome de insensibilidad androgénica (SIA)" completo.Palabras claves: síndrome de insensibilidad androgénica, hernia inguinal, cariotipo

ABSTRACT Androgen insensitivity síndrome (AIS) is one of the causes of abnormalities in sexual differentiation (different sexual development). SIA is an X-linked genetic condition caused by an androgen receptor disorder, associated with vaginal and uterine agenesis, and the presence of testicles in women with an XY karyotype. Parents with 12-day-old neonates go to medical consultation. The reason for consultation is a mass in the right inguinal region. On physical examination: normal vital signs, active on management, reactive. A mass is observed at the level of the right inguinal region of approximately 2 cm in diameter, reducible and not painful. Female external genital with normal characteristics. The patient is referred for surgery to correct hernia defect. A cytogenetic study and blood hormone leves are indicated. Seven days after the intervention, parents came with the results of the postoperative pathological study: testicular gonadal tissue with áreas of vascular congestion and focal hemorrhage. Blood hormonal lever are normal and anormal XY male karyotype is seen. Diagnosis: the result of the karyotype is conclusive and a complete AIS is diagnosed.Keywords:androgen insensitivity syndrome, inguinal hernia, karyotype.

Síndrome de Insensibilidad Completa a Andrógenos (SICA): reporte de un caso clínico / Complete Androgen Insensitivity Syndrome (CAIS): report of a clinical case

INTRODUCTION: Complete Androgen Insensitivity Syndrome (CAIS) is a X-linked recessive disorder characterized by a complete resistance of the Androgen Receptor (AR) to androgens. As a result, affected individuals present complete female external genitalia, but are genetically male with a 46, XY karyotype. The typical presentation for this syndrome is either inguinal swellings in a new born or infant, or primary amenorrhoea in an adolescent. CAIS is commonly diagnosed in one of these clinical scenarios, although recently prenatal diagnosis has been reported. We present a case of a phenotypically female infant with an inguinal swelling, which was biopsied and exposed as testicular tissue, doing the diagnosis of CAIS. A review of the literature on this disorder is made.

Complete Androgen Insensitivity Syndrome and Literature Review / Síndrome da insensibilidade androgênica completa e revisão de literatura

BACKGROUNG: Complete Androgen Insensitivity Syndrome (CAIS) has been reported since 1923, but in 1953 it became known as "testicular feminization". It is a rare recessive genetic disorder linked to the X chromosome that results in different mutations in the androgen receptor. The main clinical presentation in childhood is the presence of bilateral inguinal hernia in phenotypically female subjects. Incidence of androgen insensitivity syndrome in phenotypically females with inguinal hernia is estimated in 0.8% to 2.4%. This is a case report of complete androgen insensitivity syndrome and literature review of preoperative diagnostic methods. CASE SUMMARY: We present a 3 years and 6 months old child with female phenotype, born in São Paulo, Brazil which was diagnosed intraoperatively with complete androgen insensitivity syndrome, during inguinal hernia repair and present potential diagnostic alternatives that we consider viable options in order to avoid this kind of surprise during surgery. CONCLUSION: Investigation of CAIS should be standard in pre-pubertal girls with bilateral inguinal hernia, genetic techniques involving X chromatin or Y chromosome tests present the best choices.

INTRODUÇÃO: A síndrome da insensibilidade androgênica completa (SIAC) é relatada desde 1923, mas foi em 1953 que ficou conhecida como "feminilização testicular". É uma doença genética recessiva rara, ligada ao cromossomo X, causando diversas mutações no receptor de androgênio. A principal apresentação clínica na infância é a presença de hérnia inguinal bilateral em indivíduos fenotipicamente femininos com uma incidência estimada de 0,8% a 2,4%. Apresentamos um caso de insensibilidade androgênica completa, com revisão de literatura dos métodos diagnósticos pré operatórios. Relato do Caso: Apresentamos uma criança de 3 anos e 6 meses de idade com fenótipo feminino, nascida em São Paulo, Brasil diagnosticada com síndrome da insensibilidade androgênica completa, durante a cirurgia de herniorrafia inguinal bilateral e apresentamos potenciais alternativas diagnósticas a fim de evitar esse tipo de surpresa durante a cirurgia. CONCLUSÃO: Em meninas pré-puberes, portadoras de hérnia inguinal bilateral, a pesquisa de SIAC se faz necessária, técnicas genéticas que utilizam a pesquisa da cromatina X ou do cromossomo Y seriam as melhores escolhas.

Androgen insensitivity syndrome: a review

ABSTRACT Androgenic insensitivity syndrome is the most common cause of disorders of sexual differentiation in 46,XY individuals. It results from alterations in the androgen receptor gene, leading to a frame of hormonal resistance, which may present clinically under 3 phenotypes: complete (CAIS), partial (PAIS) or mild (MAIS). The androgen receptor gene has 8 exons and 3 domains, and allelic variants in this gene occur in all domains and exons, regardless of phenotype, providing a poor genotype - phenotype correlation in this syndrome. Typically, laboratory diagnosis is made through elevated levels of LH and testosterone, with little or no virilization. Treatment depends on the phenotype and social sex of the individual. Open issues in the management of androgen insensitivity syndromes includes decisions on sex assignment, timing of gonadectomy, fertility, physcological outcomes and genetic counseling.

Phenotypic and molecular characteristics of androgen insensitivity syndrome patients / 亚洲男科学杂志(英文版)

Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel (c.2112 C>G[p.S704R], c.2290T>A[p.Y764N], c.2626C>T[p.Q876X], c.933dupC[p.K313Qfs∗28], and c.1067delC[p.A356Efs∗123]); the other five were previously reported (c.1789G>A[p.A597T], c.2566C>T[p.R856C], c.2668G>A[p.V890M], c.2679C>T[p.P893L], and c.1605C>G[p.Y535X]). Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% (3/10) of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.

Psychological experience of patients with androgen insensitivity syndrome in the process of diagnosis and treatment: a qualitative study / 现代临床护理

Objective To explore the true feelings and emotional needs of the patients with androgen insensitivity syndrome (AIS) during diagnosis and treatment. Methods In this qualitative study, the phenomenological research method was conducted among 9 patients with androgen insensitivity syndrome. The data were analyzed by using Colaizzi analysis method. Result The AIS patients during the diagnosis and treatment experienced six psychological feelings: eagerness to understand disease knowledge, gender cognition disorder inferiority, self-pity, anger and resentment, feeling at a loss about future, general symptoms, and anxiety for social acceptance. Conclusions Nurses should provide relevant information guidance and emotional support to alleviate patients'negative emotions and enhance their confidence in the treatment. The nurses should encourage family members of the patients to participate in psychological counselling, expand social support through multiple channels, correct patients'psychological biases, and restore their self-confidence.

Two Korean girls with complete androgen insensitivity syndrome diagnosed in infancy

Androgen insensitivity syndrome (AIS) is a rare genetic disease caused by various abnormalities in the androgen receptor (AR). The AR is an essential steroid hormone receptor that plays a critical role in male sexual differentiation and development and preservation of the male phenotype. Mutations in the AR gene on the X chromosome cause malfunction of the AR so that a 46,XY karyotype male has some physical characteristics of a woman or a full female phenotype. Depending on the phenotype, AIS can be classified as complete, partial or mild. Here, we report 2 cases of complete AIS in young children who showed complete sex reversal from male to female as a result of AR mutations. They had palpable inguinal masses and normal female external genitalia, a blind-end vagina and absent Müllerian duct derivatives. They were both 46,XY karyotype and AR gene analysis demonstrated pathologic mutations in both. Because AIS is inherited in an X-linked recessive manner, we performed genetic analysis of the female family members of each patient and found the same mutation in the mothers of both patients and in the female sibling of case 2. Gonadectomy was performed in both patients to avoid the risk of malignancy in the undescended testicles, and estrogen replacement therapy is planned for their adolescence. Individuals with complete AIS are usually raised as females and need appropriate care.

Phenotypic and molecular characteristics of androgen insensitivity syndrome patients / 亚洲男科学杂志(英文版)

Androgen insensitivity syndrome (AIS), an X-linked recessive genetic disorder of sex development, is caused by mutations in the androgen receptor (AR) gene, and is characterized by partial or complete inability of specific tissues to respond to androgens in individuals with the 46,XY karyotype. This study aimed to investigate AR gene mutations and to characterize genotype-phenotype correlations. Ten patients from unrelated families, aged 2-31 years, were recruited in the study. Based on karyotype, altered hormone profile, and clinical manifestations, nine patients were preliminarily diagnosed with complete AIS and one with partial AIS. Genetic analysis of AR gene revealed the existence of 10 different mutations, of which five were novel (c.2112 C>G[p.S704R], c.2290T>A[p.Y764N], c.2626C>T[p.Q876X], c.933dupC[p.K313Qfs*28], and c.1067delC[p.A356Efs*123]); the other five were previously reported (c.1789G>A[p.A597T], c.2566C>T[p.R856C], c.2668G>A[p.V890M], c.2679C>T[p.P893L], and c.1605C>G[p.Y535X]). Regarding the distribution of these mutations, 60.0% were clustered in the ligand-binding domain of AR gene. Exons 1 and 8 of AR gene each accounted for 30.0% (3/10) of all mutations. Most of the truncation mutations were in exon 1 and missense mutations were mainly located in exons 4-8. Our study expands the spectrum of AR gene mutations and confirms the usefulness of AR gene sequencing to support a diagnosis of AIS and to enable prenatal or antenatal screening.

Complete androgen insensitivity syndrome associated with vesical fistula:a case report and literature review / 北京大学学报(医学版)

Androgen insensitivity syndrome (AIS) is a very uncommon genetic disorder that results from the resistance of androgen receptor (AR) to androgen, which influences the formation of the male genitalia and in turn presents with female phenotype.Surgical resection of undesceaded testicle and different kinds of genitoplasty are crucial methods to correct the deformity of reproductive system, as well as hormone replacement therapy, which is an essential therapy for postoperational rehabilitation in AIS patients.A 43-year-old patient, who was socially female, was first admitted to gastroenterology department due to recurrent ascites and occasional abdominal pain with unknown origin.Taking physical examination, ultrasonography, karyotype analysis and sex hormone levels into consideration, the overall manifestations revealed the typical clinical features of complete androgen insensitivity syndrome.After that she was transferred to urology department for laparoscopic gonadectomy.During the surgery, doctors found that there was a vesical fistula on the upper wall near the conjunction between the bladder and ligamenta umbilicale medium, which explained the recurrent ascites for more than 4 years.After resecting the testicles and the tissues around the vesical fistula for histopathology, the result suggested Sertoli cell adenoma, hyperplastic Leydig cells and urothelium atypical hyperplasia.Hormone replacement therapy was given right after discharge.The hormone levels of follicle-stimulating hormone, luteinizing hormone, estradiol and progesterone were modulated by the dysfunction of androgen production after gonadectomy and hormone replacement therapy together with psychotherapy could stabilize her hormone levels and improve the quality of her life.The patient was suspicious of AIS family history and the pedigree was made to analyze her family which was possibly X-linked recessive pattern.We propose three possible hypotheses of the fistula, which are direct surgical injury, recurrence of bladder cancer and congenital urachal anomalies.But whether it is relevant between urachal anomalies and AIS is yet to be discovered.

A novel mutation of the androgen receptor gene causes androgen insensitivity syndrome:a case report and literature review / 中华实用儿科临床杂志

Objective To explore the mutation of androgen receptor(AR)gene in a patient with 46,XY disorder of sex development(DSD)and to improve the diagnostic level and understanding of androgen insensitivity syndrome(AIS).Methods The clinical data of the child was analyzed,including physical examination,relevant laboratory examination,karyotype,pelvic B ultrasound,pelvic magnetic resonance imaging(MRI)and AR gene mutation.The peripheral blood of the child and his parents were drawn,and peripheral blood DNA was extracted.The polymerase chain reaction(PCR)-DNA sequencing method was used to amplify all exons of the AR gene in the child and his parents.Then,they were directly sequenced.Results A 7-years and 2-months old child who suffered from DSD,revealed physical examination that the child had normal female external genitalia,as the clitoris length was 2.0 cm×0.8 cm,with visible vaginal opening,and there were masses at bilateral inguinal region,with a size of 1.5 cm×0.8 cm.The results of human chorionic gonadotropin(HCG)stimulation test:testosterone was 0 nmol/L,androstenedione was 1.78 nmol/L,dihydrotestosterone was 0.07 nmol/L before HCG was injected;but testosterone was 4.69 nmol/L,androstenedione was 2.10 nmol/L,dihydrotestosterone was 0.33 nmol/L after HCG was injection.Sex chromosome analysis reported 46,XY karyotype.Pelvic B ultrasound revealed the absence of a uterus and ovaries and the presence of bilateral testes like gonad at each side of internal inguinal ring,with a size of 1.4 cm×1.0 cm×0.8 cm in the left,1.5 cm×0.7 cm×0.8 cm in the right;but the kidney,ureter,urinary bladder,adrenal gland and retroperitoneal for B ultrasound revealed no abnormality.Pelvic MRI(non-enhanced and enhanced)showed the presence of a blind ending vagina between rectum and urinary bladder(40 mm in depth)and the absence of uterus and ovarian tissue.DNA sequencing found one c.1685T>C heterozygous mutation(p.Ile562Thr)on exon 2 of AR gene in the child.But retrieving and summarzing documents of the domestic and foreign information databases and websites,the locus mutation of AR gene had never been reported.The structure prediction of the mutated protein(Polyohen2 and SIFT software)was significantly changed.By verifying the locus site of the parents of this child,it was found that his mother carried the same mutation,but his father was found to be normal.Conclusions A c.1685 T>C mutation(p.Ile562Thr)on exon 2 of AR gene is a novel mutation.Combined with the patient's clinical manifestations and computer prediction results,it may suggest that the novel mutation of AR gene can lead to the occurrence of AIS.