Characterization of gene rearrangements and gene conversion events in the 21-hydroxylase gene.

Congenital adrenal hyperplasia (CAH) is an inherited disorder of steroidogenesis with a wide spectrum of expression. In about 95% of cases, the disease is the result of 21-hydroxylase deficiency, an autosomal recessive condition that maps to the major histocompatibility complex (MHC) on 6p21.3 (1). Classical CAH results in excessive androgen production. Females with this disorder are frequently diagnosed at birth because of ambiguous development of external genitalia, whereas males may not present until age 4-7 when they begin to manifest inappropriate virilization. Approximately 30% of individuals with classical CAH have this simple virilizing form of the disease. The remaining 70% in addition manifest the potentially life-threatening salt-wasting form of classical CAH characterized by an inability to retain dietary sodium.

External quality assessment of rapid prenatal detection of numerical chromosomal aberrations using molecular genetic techniques: 3 years experience.

OBJECTIVES: Prenatal diagnosis using rapid molecular genetic techniques is now a widely used method for detecting the most prevalent chromosomal aneuploidies. The object of this work was to develop a methodology for delivering external quality assessment (EQA) appropriate to the needs of routine diagnostic testing laboratories. METHODS: We have provided three rounds of EQA using 15 different samples over 3 years. The scheme has developed to assess both the genotyping accuracy of the results and the appropriateness of the clinical reports issued to the referring clinician. RESULTS: Participation in the EQA scheme has increased from 9 to 27 laboratories from across Europe over the three sample distributions. All laboratories have used quantitative fluorescence-PCR (QF-PCR) to analyse these samples except for a sole participant in 2006 who used multiplex ligation-dependent probe amplification (MLPA). In total 265 samples have been distributed, of which four (1.5%) were not reported due to technical failures and one (0.4%) was reported incorrectly and must be regarded as a genotyping error. CONCLUSIONS: We have demonstrated a significant and increasing demand for EQA in the rapid detection of aneuploidies in UK and other European laboratories. Using the methodologies described, we have had a very low rate of technical failures and demonstrated a high level of genotyping accuracy. However, the quality of the clinical reports was variable and suggestions are made for improvement.