MOLECULAR DEFECTS OF ANDROGEN I RECEPTOR GENE IN PATIENTS WITH ANDROGEN INSENSTIVITY SYNDROME

Abstract

The birth of a child with ambiguous genitalia is considered a medical emergency, which should I

be solved as early as possible. Management is based on proper diagnosis. The provisional

diagnosis of DSD is based on clinical examination, cytogenetic studies, hormonal evaluation,

I imaging study and laparoscopic examination. In most of cases, the final definitive diagnosis can

not be achieved except by molecular methods.

The spectrum of DSD comprises three main groups, abnormal gonadal differentiation, 46,XX

DSD and 46,XY DSD. Among 46,XY DSD patients, 5aR2 deficiency and androgen insensitivity '

are the most common etiologies.

Androgen action in human beings is dependant, to a large extent on the binding of the ligand, T

or its biologically active reduced form, Dl-lT to its receptor, the AR in target cells (Migcon eta/., 1994). This binding leads to the initiation of a cascade of events leading ' to a variety of changes in androgen responsive tissues. AlS is an X-linked recessive disorder whose molecular mechanism IS due to reductior or absence of androgen signaling caused by AR malfunction or absence. The aim of this work is to delineate the molecular defects in Egyptian patients with AR defect

among cases of 46,XY DSD and to evaluate the molecular studies as a tool for diagnosis of D' SD

cases.

111e present study comprised 23 patients of 46,XY DSD due to androgen resistance who W'

ere

referred to the Clinical Genetic Department, liGGRD, National Research Center complainin!' of

ambiguous genitalia.

The patients were subjected to:-

; Full clinical assessment including evaluation of the external genitalia using a number of published scoring systems.