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.

Clinical Characteristics and Genotype-Phenotype Correlation of Korean Patients with Spinal and Bulbar Muscular Atrophy

PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease characterized by proximal muscle weakness, muscle atrophy, and fasciculation. Although SBMA is not uncommon in Korea, there is only one study reporting clinical characteristics and genotype-phenotype correlation in Korean patients. MATERIALS AND METHODS: In this study, age at the onset of symptoms, the score of severity assessed by impairment of activities of daily living milestones, and rate of disease progression, and their correlations with the number of CAG repeats in the androgen receptor (AR) gene, as well as possible correlations among clinical characteristics, were analyzed in 40 SBMA patients. RESULTS: The median ages at onset and at diagnosis were 44.5 and 52.5 years, respectively, and median interval between onset and diagnosis and median rate of disease progression were 5.0 years and 0.23 score/year, respectively. The median number of CAG repeats in the AR gene was 44 and the number of CAG repeats showed a significant inverse correlation with the age at onset of symptoms (r=-0.407, p=0.009). In addition, patients with early symptom onset had slower rate of disease progression. CONCLUSION: As a report with the largest and recent Korean cohort, this study demonstrates clinical features of Korean patients with SBMA and reaffirms the inverse correlation between the age at disease onset and the number of CAG repeats. Interestingly, this study shows a possibility that the rate of disease progression may be influenced by the age at onset of symptoms.

Polycystic ovary syndrome woman with heterozygous androgen receptor gene mutation who gave birth to a child with androgen insensitivity syndrome

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is a multifactorial polygenic disorder with a broad spectrum of clinical manifestations. Although pathogenesis is still unclear, androgen receptor (AR) gene polymorphism may be one of the etiologic factors of PCOS. AR gene polymorphism has been also associated with other forms of androgen pattern diseases. We report a PCOS woman with heterozygous AR gene mutation who gave birth to a baby with andorgen insensitivity syndrome.

Associations between androgen receptor CAG & GGN repeat polymorphism & recurrent spontaneous abortions in Chinese women.

Background & objectives: Recurrent spontaneous abortion (RSA) is a reproductive problem that occurs in women in reproductive age with a frequency of 1-3 per cent. Previous studies have reported high levels of serum androgens to be associated with RSAs. At the molecular level, the effect of androgens is mediated through the activation of the androgen receptor (AR). The CAG and GGN repeat polymorphisms of the AR gene are associated with the AR activity. We hypothesize that the AR CAG/GGN repeat polymorphism may be associated with levels of serum androgens. Thus, this study as undertaken to evaluate the relationship between CAG/GGN repeats in exon 1 of the AR gene in women with RSAs. Methods: This case-control study was performed in Ningxia, PR China, including 149 women with RSAs and 210 controls. The CAG and GGN repeats of the AR gene were genotyped using a PCR-based assay and were analyzed using Peak Scanner Software v1.0 to determine the CAG/GGN repeat length. Results: CAG repeats ranged from 15 to 29 in the RSA patients, compared to 14 to 35 in the control group. The median value of CAG repeats was 22 for the RSA group and 24 for control group. The total AR CAG alleles (≤22 repeats), shorter AR CAG alleles (≤22 repeats), and biallelic means (≤22.5 repeats) were significantly different in the RSA group in comparison to the control group (P<0.001, P<0.01). The median value of the GGN repeats was 23 for the cases and 22 for controls. The total number of AR GGN alleles (≤23 repeats) was significantly different in the RSA group compared to the control group (pP<0.5). There was no difference between the RSA group and the control groups in regards to shorter alleles, longer alleles, and biallelic means. Interpretation & conclusions: Our observation suggests that the CAG and GGN repeat length is shorter in women with RSAs as compared with controls and that shorter CAG and GGN repeats may be pathogenic for RSAs in Chinese women. Further studies need to be done in different ethnic populations.

Clonality analysis of Kaposi's sarcoma lesions by human androgen receptor assay / 中华皮肤科杂志

Objective To analyze the clonality in Kaposi's sarcoma (KS) lesions by evaluating Xchromosome inactivation pattern in the human androgen receptor (HUMARA) gene.Methods Twenty-five paraffinembedded tissue specimens were collected from female patients with KS (n =15) or cutaneous hemangioma (n =10).DNA was extracted from these specimens,and digested with the methylation-sensitive restriction endonuclease Hpa Ⅱ.PCR was performed to amplify the HUMARA gene,and the amplicons were separated on a 10％ denaturing polyacrylamied gel and stained with ethidium bromide (EB).The loss of heterozygosity of the HUMARA gene was defined as the presence of two DNA fragments before and one fragment after the endonuclease digestion.The clonality in KS lesions was assessed based on the above results.Results Among the 15 patients with KS,13 (86.7％) were heterozygous for the HUMARA gene,of which,92.31％ (12/13) showed loss of heterozygosity of the HUMARA gene on X-chromosome,suggesting a monoclonal origin.Of the 10 patients with hemangioma,9 were heterozygous for the HUMARA gene,and only one lost heterozygosity of the HUMARA gene.The heterozygosity rate for HUMARA gene was significantly different between the patients with KS and hemangioma (P ＜ 0.01).No statistical difference was observed in the clonality status of KS between patients of different nationality,at different stages,or between patients with and without complicated human immunodeficiency virus (HIV) infection (all P ＞ 0.05).Conclusion KS is monoclonal in origin.

A clinical, pathological and genetic study of a Chinese family with Kennedy disease / 第二军医大学学报

Objective: To report a genetically proven Kennedy disease pedigree in China and to discuss its clinical presentations, pathological features and molecular mechanism, so as to provide more information on Kennedy disease. Methods: We conducted a complete survey of the family, including 3 generations and 41 individuals. The proband was given a thorough clinical examination including CK level, EMG, testosterone level, nerve biopsy, and muscle biopsy. Genomic DNA was extracted from the peripheral blood; the repeats of CAG in the exon 1 of androgen receptor was amplified by PCR and sequenced directly. Results: The sequencing result showed that the proband(III-11) had a CAG repeat of 54); one patient (IV-2) had a CAG repeat of 55; one had a CAG repeat of 54; one presymptomatic individual had a CAG repeat of 54(IV-8). There were 3 female carriers (II-6, III-3, and III-15). The CPK and testosterone levels were increased in the proband. EMG revealed neurogenic injury. Nerve biopsy revealed demylination change in the peripheral nerve and muscle biopsy revealed muscle atrophy originated from nerve. Conclusion: Kennedy has no characteristic clinical symptoms, and gene diagnosis is the gold standard. The progression of SBMA is usually much slower compared with those of bulbar atrophy and atrophic lateral sclerosis(ALS).

Evaluación del patrón de inactivación del cromosoma X en portadoras sintomáticas y mujeres con hemofilia / Assessing the inactivation pattern in chromosome X among symptomatic carriers and women with haemophilia

La inactivación del cromosoma X es un fenómeno estocástico que ocurre en la embriogénesis temprana femenina para lograr una compensación de dosis génica respecto a los varones. Ciertos mecanismos genéticos afectan el proceso normal, propiciando una inactivación sesgada con efectos clínicos relevantes en portadoras de trastornos recesivos ligados al cromosoma X, como la hemofilia. La herramienta molecular mayormente utilizada para la evaluación del patrón de inactivación del cromosoma X es la amplificación por PCR del gen del receptor de andrógenos humano (HUMARA). El empleo de esta técnica en portadoras sintomáticas y mujeres con hemofilia permite esclarecer si las manifestaciones de la enfermedad se deben a una lyonización desfavorable. Estos estudios, además, son importantes para la comprensión del proceso de inactivación del cromosoma X en humanos.

X chromosome inactivation is a stochastic event that occurs early in female embryo development to achieve dosage compensation with males. Certain genetic mechanisms affect the normal process causing a skewed X inactivation pattern which has clinical relevance in female carriers of X-linked recessive disorders, like haemophilia. The most commonly used assay to evaluate the X inactivation pattern is the PCR amplification of the human androgen receptor gene (HUMARA). The use of this technique in bleeding carriers and women with haemophilia allows identifying if their hemorrhagic symptoms are due to an unfavourable lyonization. Furthermore, these studies are important for understanding the X chromosome inactivation process in humans.

Complete androgen insensitivity syndrome due to androgen receptor gene mutation in the amino acid position 607 which bilateral testes situated in the normal ovary sites / 대한산부인과학회지

Androgen insensitivity syndrome (AIS) is a disorder of male sexual differentiation caused by mutations within the androgen receptor gene, represents a variety of phenotypes from females with 46,XY karyotype over individuals with ambiguous genitalia to infertile males. Single base mutations resulting in amino acid substitution represent the most common mutations of the androgen receptor (AR) gene and are associated with complete AIS. The location of the gonads can be variable including, the intra-abdominal cavity, the labioscrotal folds, and the inguinal regions. Testicular descent is a two-stage process comprising transabdominal and transinguinal phases. The first phase is not controlled by androgen and may be regulated by mullerian inhibiting substance, by contrast the second phase is androgen dependent. Recently we have identified a point mutation CGA to TGA at position 607 of exon 3 in complete AIS patient, so we report it with brief review of literatures.

Association of Gonadal Receptor Genes′ Microsatellites and Dysfunctional Attitudes in Adolescent with Major Depressive Disorder / 实用儿科临床杂志

Objective To explore the associations between microsatellites in gonadal receptor genes and dysfunctional attitudes in adolescent with major depressive disorder(MDD).Methods Polymerase chain reaction(PCR),capillary electrophoresis and genetic scanning were performed in testing the length of microsatellites in first-onset adolescent depressive patients.Dysfunctional attitudes scale(DAS) was used in rating the dysfunctional cognition of adolescent depressive sample.These results were tested by correlative analysis and comparison analysis.Results 1.There existed significantly negative correlation between microsatellite′s length in estrogen receptor ?(ER?) gene and total score of DAS in female adolescent patients with first-onset depressive disorder.2.DAS′ total score of shorter alleles′ group was significantly higher than that of longer alleles′ group on female′ estrogen receptor ?(ER?) Gene.Conclusion The microsatellite′s length of ER? and ER? gene may have associations with dysfunctional attitudes of female adolescent with MDD.

Preliminary study of relationship between the CAG repeat polymorphism of androgen receptor gene and benign prostatic hyperplasia in Xinjiang Uygur men / 中华泌尿外科杂志

0.05).But the association between (CAG)n repeats and prostate volume was significant (P

Analysis of Androgen Receptor Gene in Korean Patients with Androgen Insensitivity Syndrome / 대한산부인과학회잡지

Androgen insensitivity syndrome (AIS) is a X-linked disorder of sexual differentiation resulting from defective androgen receptor (AR) function. Androgens are secreted by the testes of 46,XY individuals, but there is loss of target organ response to the hormone. The abnormalities of AR are due to defects in the AR gene, and many mutations causing AIS have been reported since the cloning of AR gene. In this study, we analyzed the AR genes in twelve Korean patients with androgen insensitivity syndrome: 9 patients with complete AIS and 3 patients with partial AIS DNAs were isolated from patients with AIS, and the coding region of AR gene was amplified by a polymerase chain reaction using 7 pairs of primers (exon B-H). Sequence analysis of the AR gene was performed using direct sequencing and single strand conformational polymorphism (SSCP). The AR gene mutations were identified in 7 out of 12 patients: 6 of 9 patients with complete AIS, and one of 3 patients with partial AIS. Mutations found were as follows: the point mutation (ATT->ACT) at position 680 of exon D, point mutation (TGG->TGC) at position 751 of exon E, point mutation (CAA->TAA) at position 792 of exon F, point mutations (CGC->TGC, GTG->ATG) at position 855 and 866 of exon G, and the deletion of 13 nucleotides (CGTATCATTGCAT) at position 840 of exon G, respectively. To the best of our knowledge, the point mutations found in exon D, exon E, and exon F, and the deletion in exon G have not been observed before. SSCP revealed bands with abnormal mobility in 10 out of 12 patients tested. Mutations were found 5 out of these 10 patients. The other two patients showed no abnormal band on SSCP, but showed mutations by direct sequencing. In conclusion, we have demonstrated the AR gene mutations, including three novel mutations, in Korean patients with AIS, and these abnormalities might be related to the pathogenesis of androgen insensitivity syndrome.