Novel CYP11B1 Mutations in Congenital Adrenal Hyperplasia due to Steroid 11 -Hydroxylase Deficiency

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Abstract
The second,most,common,cause of congenital,adrenal,hyperplasia is 11b-hydroxylase deficiency, an autosomal recessive disorder. We performed genetic analysis of CYP11B1, the gene encoding steroid 11b-hydroxylase, in three patients with classic 11b-hydroxylase de- ficiency. Herein we describe the first splice donor site mutation, a new nonsense mutation, and a new missense mutation in this disorder. An African-American,patient was,found,to be a compound,heterozygote for a codon,31811G3 A substitution,at the 59-splice donor,site of intron 5, in combination with Q356X, a nonsense mutation previously reported,in an African-American,patient. A Caucasian,patient,was found to be a compound heterozygote with a novel missense mutation, T318R, in combination with a previously reported 28-bp deletion in exon 2. A different mutation,at codon 318 (T318M) has been described previously. A Caucasian,patient,was,heterozygous,for a novel non- sense mutation,(Q19X) in exon 2. The second,mutation,was not iden- tified in this patient. Multiple apparent,polymorphisms,were,also observed. Two of these,polymorphisms,in CYP11B1 represent,se- quences from CYP11B2, suggesting that gene conversion may have occurred. In summary, we have identified three novel mutations and two previously,reported,mutations,in CYP11B1 patients,with,11b- hydroxylase,deficiency. Our data suggest,the presence,of a mutational hot spot at codon 318 of CYP11B1, and the possibility of a founder effect in frequently,identified mutations. (J Clin Endocrinol Metab 83: 270 ‐273, 1998) C ONGENITAL adrenal,hyperplasia,(CAH) denotes,a

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