Identification of the Underlying Androgen Receptor Defect in the Dallas Reifenstein Family.

CONTEXT: The Dallas Reifenstein family - first described in 1965 - includes 14 known members with partial androgen insensitivity syndrome (PAIS). However, the underlying molecular defect was never identified. OBJECTIVE: To identify the underlying genetic defect for PAIS in the Dallas Reifenstein family. DESIGN: DNA was purified from scrotal skin fibroblasts, and whole exome sequencing was then performed in four affected men in the family. Additional family members - both affected and unaffected - were subsequently recruited to confirm segregation of the candidate mutations with the PAIS phenotype. PATIENTS: The affected men have PAIS with infertility associated with azoospermia, hypospadias, and gynecomastia. RESULTS: All four men harbored an intronic variant NC_000023.10:g.66788676A>C between exon 1 and exon 2 of the androgen receptor (AR) canonical transcript NM_000044 (complementary DNA position NM_000044: c.1616+22072A>C) predicted to cause an alternatively spliced AR transcript. Reverse transcription (RT) polymerase chain (PCR) experiments detected the predicted PCR product of the alternatively spliced AR transcript, and the mutation segregated with the PAIS phenotype in this family. The transcript includes the insertion of 185 nucleotides with a premature stop codon at chrX:66863131-66863133, likely resulting in a reduction in AR protein expression due to nonsense-mediated decay. CONCLUSIONS: An intronic AR mutation was identified in the Dallas Reifenstein family. The findings suggest that in cases of PAIS without identifiable AR mutations in coding regions, intronic AR mutations should be considered.

Incomplete androgen insensitivity (Reifenstein syndrome) - a case report.

We report a 20 year old case of partial androgen insensitivity syndrome, referred to our clinic with complaints concerning external genital organs and left undescended testicle. The phenotypically male case was first evaluated for secondary sex development. Axillary hair was scanty and no pubic hair was found. There was no breast development. In the gynecological examination, the clitoris was hypertrophic (4.6 cm) and a blind vagina with intact hymen was seen. Abdominopelvic ultrasonography revealed the absence of an uterus and adnexes which was supported by magnetic resonance imaging (MRI). There was a palpable mass in the left inguinal canal (cryptorchism), seen as atrophic tissue under the skin in MRI. Although the other testis was in the labioscrotal fold, it was atrophic. The Karyotype was 46 XY after genetic investigation.

Neovaginoplasty Using Sigmoid Colon in Patient with Male Pseudo-hermaphroditism / 대한비뇨기과학회지

Gender assignment is the most important step in treating a child with ambiguous genitalia. Once an appropriate sex assignment has been made, the next critical step is the performance of a reconstructive procedure in a timely fashion. The aim of vaginoplasty should be the creation of a neovagina that will have a satisfying appearance, function and feeling, with a low rate of morbidity. Different forms of vaginal reconstruction have been described, and include the use of split-thickness or full-thickness grafts, amnion, peritoneum or bowel. Of these, vaginal reconstruction, with isolated bowel segments, provides a cosmetic, self-lubricating neovagina, with low rates of failure and revision, and without the need for routine dilation. Sigmoid vaginoplasty especially seems to have a clear advantage, with an excellent surgical success rate, and low complication rates. We report our initial experience of a neovaginoplasty, using sigmoid colon, in a 10-year old patient with an incomplete form of androgen insensitivity syndrome (Reifenstein syndrome).