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Molecular prenatal diagnosis of partial androgen insensitivity syndrome based on the Hind III polymorphism of the androgen receptor gene *
Author(s) -
Lobaccaro JeanMarc,
Belon Charles,
Lumbroso Serge,
Olewniczack Georges,
CarréPigeon Françoise,
Job JeanClaude,
Chaussain JeanLouis,
Toublanc JeanEdmond,
Sultan† Charles
Publication year - 1994
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1994.tb03922.x
Subject(s) - androgen receptor , complete androgen insensitivity syndrome , androgen insensitivity syndrome , androgen , restriction fragment length polymorphism , biology , endocrinology , medicine , fetus , prenatal diagnosis , gene , genetics , pregnancy , genotype , hormone , cancer , prostate cancer
Summary OBJECTIVE Partial androgen Insensitivity syndromes are the cause of genital ambiguity that is at times quite severe; there is, therefore, a high demand for prenatal diagnosis in families already afflicted with this syndrome. When the mutation has not been identified, the diagnosis can be made by the study of the polymorphisms of the androgen receptor gene. To perform molecular prenatal diagnosis in a family with partial androgen insensitivity syndrome, we studied the Hind III polymorphism of the androgen receptor gene on the trophoblastic DNA. The use of this restriction fragment length polymorphism tracked maternal X chromosome segregation and established prenatal diagnosis although the mutation had not yet been identified in this family. FAMILY The mother had been previously described as heterozygous for the Hind III polymorphism and chromosomal segregation analysis showed that the affected allele was associated with the 6.7‐kb Hind III fragment. MEASUREMENTS Hind III RFLP with an androgen receptor gene cDNA probe was realized on the trophoblastic DNA, along with measurement of androgen binding activity on the trophoblastic cells. RESULTS We detected the presence of the 6.7‐kb fragment In the DNA of the trophoblastic cells suggesting the fetus was affected. Partial androgen insensitivity syndrome was confirmed by a considerable decrease in androgen binding activity on the trophoblastic cells and by sonography of the fetus. After a therapeutic abortion requested by the parents, the diagnosis was confirmed by clinical examination of the fetus, biochemical analyses of the fetal androgen receptor, and molecular studies of the fetal DNA. CONCLUSIONS When the mutation of the androgen receptor gene has not been identified, Hind III polymorphism of the trophoblastic DNA is useful in the prenatal diagnosis of androgen insensitivity syndrome in high‐risk families.