A rapid screening for steroid 21-hydroxylase mutations in patients with congenital adrenal hyperplasia. Mutations in brief no. 247. Online.
Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia (CAH). CAH due to 21-hydroxylase deficiency is divided into three classes: salt-wasting (classical), non-classical and simple virilizing, reflecting different degrees of clinical severity. Using polymerase chain reaction (PCR) and allele-specific oligonucleotide hybridisation (ASO), we screened the DNA of 62 Caucasian CAH families (heterozygous parents and children) for 14 different and frequently-found CYP21-mutations (HGMD). Of the 62 patients (21 males, 41 females), 26 females and 11 males had the classical or salt-wasting form, 3 females and 1 male had the non-classical form and 14 females and 7 males had simple virilizing CAH. More than 60% of the patients were compound-heterozygous. We found the mutations on 110 alleles (out of 124 alleles). There were 30 CYP21 gene deletions/conversions, 3 substitutions (P30L) in exon 1, 30 splice mutations (c.93-13A/C>G) in intron 2, 26 point mutations (I172N) in exon 4, one cluster of mutations (I236N, V237E, M239K) in exon 6, 8 mutations (V281L and 1760-1761insT) in exon 7, and 8 nonsense (Q318X) and 4 missense (R356W) mutations in exon 8. Our study supports the case for using this rapid technique for CAH-family screening as long as alleles from both affected patients and parents are screened in parallel.
Institute for General and Experimental Pathology, Department of Molecular Pathophysiology, University of Innsbruck Medical School, Austria.
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Kapelari
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Ghanaati
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Wollmann
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Ventz
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Ranke
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Kofler
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Peters
D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics*; D000483:Alleles; D017398:Alternative Splicing; D005260:Female; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D013255:Steroid 21-Hydroxylase