TY - JOUR
T1 - Who is a carrier? Detection of unsuspected mutations in 21-hydroxylase deficiency
AU - Witchel, Selma Siegel
AU - Lee, Peter A.
AU - Trucco, Massimo
PY - 1996/1/2
Y1 - 1996/1/2
N2 - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common autosomal-recessive disorder. During our routine genotyping of affected individuals and their relatives using allele-specific oligonucleotide hybridization and single-strand conformational polymorphism analysis, we identified two families each segregating three mutations. In both families, a mutation known to be associated with 21-hydroxylase deficiency was identified in healthy individuals but was not detected in the propositus. The propositus in family 1 was shown to be a homozygous carrier for G at nucleotide 655, which alters the splice acceptor site at exon 3. The propositus in family 2 carried the same splicing mutation on the maternal allele and a gene deletion/conversion on the paternal allele. In both families, other clinically unaffected relatives carried the Q318X mutation in exon 8. If molecular diagnostic studies had been limited to the mutation carried by the propositi, relatives would have been misinformed regarding their status as carriers or mildly affected individuals. The findings in these two families emphasize the high frequency of alleles causing 21- hydroxylase deficiency in the population.
AB - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common autosomal-recessive disorder. During our routine genotyping of affected individuals and their relatives using allele-specific oligonucleotide hybridization and single-strand conformational polymorphism analysis, we identified two families each segregating three mutations. In both families, a mutation known to be associated with 21-hydroxylase deficiency was identified in healthy individuals but was not detected in the propositus. The propositus in family 1 was shown to be a homozygous carrier for G at nucleotide 655, which alters the splice acceptor site at exon 3. The propositus in family 2 carried the same splicing mutation on the maternal allele and a gene deletion/conversion on the paternal allele. In both families, other clinically unaffected relatives carried the Q318X mutation in exon 8. If molecular diagnostic studies had been limited to the mutation carried by the propositi, relatives would have been misinformed regarding their status as carriers or mildly affected individuals. The findings in these two families emphasize the high frequency of alleles causing 21- hydroxylase deficiency in the population.
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U2 - 10.1002/(SICI)1096-8628(19960102)61:1<2::AID-AJMG1>3.0.CO;2-1
DO - 10.1002/(SICI)1096-8628(19960102)61:1<2::AID-AJMG1>3.0.CO;2-1
M3 - Article
C2 - 8741909
AN - SCOPUS:0030030695
SN - 0148-7299
VL - 61
SP - 2
EP - 9
JO - American Journal of Medical Genetics
JF - American Journal of Medical Genetics
IS - 1
ER -