OBJECTIVE: To detect potential variant of AR gene in an infant with complete androgen insensitivity syndrome. METHODS: The coding regions and splicing sites of the AR gene were subjected to PCR amplification and direct DNA sequencing. Fluorescence quantitative PCR was also used to detect copy number alterations of exons 2 to 8 of the AR gene. RESULTS: Deletion of exons 2 to 8 was detected in the proband, and the results were verified among the family members. CONCLUSION Hemizygotic deletion of exons 2 to 8 of the AR gene probably underlies the complete androgen insensitivity syndrome in this infant.
Androgen-Insensitivity Syndrome ; genetics ; Base Sequence ; Exons ; Humans ; Infant ; Male ; Polymerase Chain Reaction ; Receptors, Androgen ; genetics

Adolescent ; Androgen-Insensitivity Syndrome/genetics* ; Cytosine ; Female ; Guanine ; Humans ; Male ; Mutation ; RNA Splice Sites/genetics* ; Receptors, Androgen/genetics*

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.
Adolescent ; Adult ; Androgen-Insensitivity Syndrome/genetics* ; Child ; Child, Preschool ; DNA Mutational Analysis ; Genetic Association Studies ; Humans ; Male ; Mutation, Missense ; Phenotype ; Receptors, Androgen/genetics* ; Symptom Assessment ; Young Adult

OBJECTIVETo identify potential mutation of androgen receptor (AR) gene in a patient with complete androgen insensitivity syndrome (CAIS) and his family members.

METHODSTotal RNA and genomic DNA were extracted from the peripheral blood samples derived from the proband and her family members. Sequences of 7 exons of the AR gene were amplified with reverse transcriptase PCR(RT-PCR) and subjected to direct sequencing. Suspected mutation was also analyzed with PCR-restriction fragment length polymorphism (PCR-RFLP) and direct sequencing.

RESULTSDNA sequencing has revealed a nucleotide change (2880A>G) in the pedigree, which resulted in a missense mutation (R840H).

CONCLUSIONA prenatal diagnostic method was established for detecting mutation of the AR gene in the pedigree. Long chain RT-PCR was first used for the detection of AR gene mutations.

Androgen-Insensitivity Syndrome ; genetics ; Base Sequence ; Child ; DNA Mutational Analysis ; methods ; Family Health ; Female ; Humans ; Male ; Mutation, Missense ; Pedigree ; Receptors, Androgen ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; methods

OBJECTIVETo investigate the clinical and molecular genetics characteristics of a patient with mild androgen insensitivity syndrome (MAIS).

METHODSClinical data of the patient was collected, and DNA was isolated from peripheral blood sample. Eight exons of AR gene were amplified by PCR with specific primers and directly sequenced by Sanger method. The results were compared with standard sequences from GenBank. Online Polyphen-2 software was applied to predict the effect of mutation on the protein function and compare the conservation of the sequence at the mutation site in various species. The exon of the AR gene containing the mutated site was analyzed in 90 unrelated normal males using PCR and restrictive digestion with Sfa NI.

RESULTSSequence analysis has detected a novel missense mutation in codon 176 of exon 1 (Ser176Arg) of the AR gene. Analysis with polyphen-2 software has indicated the codon to be highly conserved across various species, and that the S176A mutation has caused damage to the protein structure and function (prediction score=0.999). The same mutation was not detected in 90 healthy males.

CONCLUSIONThe S176A mutation of the AR gene may contribute to the mild androgen insensitivity syndrome.

Adult ; Amino Acid Sequence ; Androgen-Insensitivity Syndrome ; genetics ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Receptors, Androgen ; genetics

Androgen-Insensitivity Syndrome ; genetics ; Female ; Humans ; Male ; Mutation ; Pedigree ; Receptors, Androgen ; genetics

OBJECTIVETo identify potential mutation of human androgen receptor (AR) gene in a patient with complete androgen insensitivity syndrome (CAIS).

METHODSDNA sequences of 8 exons and exon/intron boundaries of the AR gene were amplified with PCR and directly sequenced.

RESULTSDNA sequencing has revealed a frameshift mutation due to deletion of nucleotide C at position 3507 in exon 6, which gave rise to a stop codon resulting premature termination for translation.

CONCLUSIONA novel frameshift mutation in exon 6 of AR gene probably underlies the disease in our patient.

Androgen-Insensitivity Syndrome ; diagnosis ; genetics ; Base Sequence ; Exons ; Frameshift Mutation ; Humans ; Male ; Phenotype ; Receptors, Androgen ; genetics ; Young Adult

OBJECTIVETo identify the mutation of human androgen receptor gene (AR) in a patient with complete androgen insensitivity syndrome (CAIS).

METHODSDNA sequences of 8 exons and their exon/intron boundaries of the AR gene in the patient were amplified by PCR and directly sequenced.

RESULTSDNA sequencing revealed a nonsense mutation in exon 1, resulting in a change of codon 441 GAA (glutamic acid) to a stop codon (TAA).

CONCLUSIONA novel mutation Glu441stop (GAA to TAA) of the androgen receptor gene leading to complete androgen insensitivity syndrome was identified in this study in a Chinese patient. It may help us further understanding the pathogenesis of CAIS.

Adult ; Androgen-Insensitivity Syndrome ; genetics ; Base Sequence ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Polymerase Chain Reaction ; methods ; Receptors, Androgen ; genetics ; Sequence Analysis, DNA ; methods

Adolescent ; Androgen-Insensitivity Syndrome ; genetics ; Female ; Humans ; Male ; Mutation ; Polymerase Chain Reaction ; Receptors, Androgen ; genetics ; Sequence Analysis, DNA

OBJECTIVETo identify the mutation of the androgen receptor (AR) gene in a complete androgen insensitivity family.

METHODSDNA was extracted from peripheral blood samples from family members in the family. PCR and DNA sequencing were then employed to detect the mutation of AR gene.

RESULTSA single nucleotide deletion of nucleotide A in exon 4 of the AR gene (1910delA) was detected in all the three patients in this family, which lead to Asn637Ile and Lys638stop. This mutation was also found in the mother (heterozygote) but was not observed in the normal controls.

CONCLUSIONThe 1910delA mutation of the AR gene is a novel mutation that leads to complete androgen insensitivity syndrome.

Androgen-Insensitivity Syndrome ; genetics ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Humans ; Male ; Molecular Sequence Data ; Pedigree ; Receptors, Androgen ; genetics ; Sequence Deletion ; genetics ; Young Adult