TY - JOUR
T1 - CYP11B1 mutations causing congenital adrenal hyperplasia due to 11β- hydroxylase deficiency
AU - Geley, Stephan
AU - Kapelari, Klaus
AU - Jöhrer, Karin
AU - Peter, Michael
AU - Glatzl, Josef
AU - Vierhapper, Heinrich
AU - Schwarz, Siegfried
AU - Helmberg, Arno
AU - Sippell, Wolfgang G.
AU - White, Perrin C.
AU - Kofler, Reinhard
PY - 1996
Y1 - 1996
N2 - Accurate knowledge of the molecular basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a prerequisite for genetic counseling, prenatal diagnosis, and treatment. Analysis of nine patients suffering from severe manifestations of this disorder led to the identification of seven novel mutations in their CYP11B1 genes. A Caucasian patient was homozygous for the missense mutation R448H, previously found only in Jews of Moroccan origin. An Iranian patient was found to be homozygous for a different mutation in the same codon, R448C. Of four unrelated patients, two were homozygous for a nonsense mutation (W247X), whereas two others were compound heterozygotes for W247X in combination with either R448H or E371G. Two other patients were homozygous for either the missense mutation A331V or an in-frame CTG insertion adjacent to codon 464 (InsCTG464). One patient was a compound heterozygote for two mutations in exon 2, a 28-bp deletion (Δ28bpEx2) and the missense mutation V129M. All of the missense mutations and the CTG insertion caused a complete loss of steroid 11β-hydroxylating activity when expressed in cultured cells. These data support previous suggestions of mutational hot spots in CYP11B1 and confirm that severe clinical manifestations are associated with complete loss of enzymatic activity.
AB - Accurate knowledge of the molecular basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency is a prerequisite for genetic counseling, prenatal diagnosis, and treatment. Analysis of nine patients suffering from severe manifestations of this disorder led to the identification of seven novel mutations in their CYP11B1 genes. A Caucasian patient was homozygous for the missense mutation R448H, previously found only in Jews of Moroccan origin. An Iranian patient was found to be homozygous for a different mutation in the same codon, R448C. Of four unrelated patients, two were homozygous for a nonsense mutation (W247X), whereas two others were compound heterozygotes for W247X in combination with either R448H or E371G. Two other patients were homozygous for either the missense mutation A331V or an in-frame CTG insertion adjacent to codon 464 (InsCTG464). One patient was a compound heterozygote for two mutations in exon 2, a 28-bp deletion (Δ28bpEx2) and the missense mutation V129M. All of the missense mutations and the CTG insertion caused a complete loss of steroid 11β-hydroxylating activity when expressed in cultured cells. These data support previous suggestions of mutational hot spots in CYP11B1 and confirm that severe clinical manifestations are associated with complete loss of enzymatic activity.
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U2 - 10.1210/jc.81.8.2896
DO - 10.1210/jc.81.8.2896
M3 - Article
C2 - 8768848
AN - SCOPUS:10144250291
SN - 0021-972X
VL - 81
SP - 2896
EP - 2901
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 8
ER -