Abstract
In 13 unrelated CAH families (2 with 2 patients) from Berlin, Germany, the CYP21B gene and its region were studied to establish if the incidence of each genetic lesion and the relationship between genotype and phenotype are similar to these of other populations. Among our families, 6 had SW, 5 SV and 2 NC form. 26 different CAH haplotypes have been analyzed using the simple strategy combining Southern blotting studies and specific amplification of the CYP21B gene by PCR as previously described (Endocri Soc 1991, abstr. 1379). To-date screening for 8 point mutations (PM) of the CYP21B gene was done. The most common lesions were large deletions (6/26, 23%) and two PM: 668-13C→G (6/26, 23%) and 1172N (5/26, 20%). Less frequent were large gene conversions (2/26, 8%) and PM G318X (1/26, 4%) and V281L (2/26, 8%). On 15% (4/26) of the haplotypes, no mutation could be found yet. A good correlation exists between genotype and phenotype. All patients homozygous or double heterozygous for large deletions, gene conversions or G318X had a SW form. 1172N was correlated with SV form in homozygous as well as in double heterozygous patients. V281L was found in 1 patient with NC form. In contrast, 668-13C-→G mutation did not correlate well with clinical expression: two homozygous patients for 668-13C→G had neonatal SW crisis, but actually, endocrine investigation shows no more SW, even without treatment. HLA typing confirmed that HLA-Bw47 (2) is associated with CYP21B large deletion; HLA Bw51, often associated with SV form in german population, was found with different genetic lesions and all phenotypes in our patients. Almost all families (11/13) were fully informative for prenatal diagnosis when determining the PM in association with our Southern appproach; the 2 remaining ones (1SV, INC) were semi-informative. This direct molecular study of the CYP21B gene could be used for prenatal diagnosis.
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Serban, A., L'Allemand, D., Helge, H. et al. RELATIONSHIP BETWEEN GENOTYPE AND PHENOTYPE TN GERMAN FAMILIES WITH CONGENITAL ADRENAL HYPERPLASIA (CAH) DUE TO 21 HYDROXYLASE DEFICIENCY. Pediatr Res 33 (Suppl 5), S16 (1993). https://doi.org/10.1203/00006450-199305001-00080
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DOI: https://doi.org/10.1203/00006450-199305001-00080