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KMID : 0377619960610020159
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Korean Jungang Medical Journal
1996 Volume.61 No. 2 p.159 ~ p.167
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Aromatase Deficiency
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Adashi, Eli Y.
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Abstract
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LEARNING OBJECTIVES
1. To appreciate the existence of aromatase deficiency in an adult female thereby recognizing that such a mutation is not necessarily lethal.
2. To appreciate the techniques employed to diagnose the precise nature of the relevant mutation.
3. To understand the implications and lessons of this "mistake" of nature.
PRESENTATION NARRATIVE SUMMARY
Two mutations in the CYP19 gene responsible for aromatase deficiency have been recognized in an 18-year-old 46,XX female with ambiguous external genitalia at birth, primary amenorrhea and sexual infantilism, and polycystic ovaries. The coding exons, namely exons II-X, of the CYP19 gene were amplified by PCR from genomic DNA and sequenced directly. Direct sequencing of the amplified DNA from the patient revealed two single-base changes, at by 1303 (C -> T) and by 1310 (G -> A) in exon X, which were newly found missense mutations and resulted in codon changes of R435C and C437Y, respectively. Subcloning followed by sequencing confirmed that the patient is a compound heterozygote. The results of restriction fragment length polymorphism analysis and direct sequencing of the amplified exon X DNA from the patient´s mother indicate maternal inheritance of the R435C mutation. Transient expression experiments showed that the R435C mutant protein had ?1.1 % of the activity of the wild type, whereas C437Y was totally inactive. Cysteine -437 is the conserved cysteine in the heme-binding region believed to serve as the fifth coordinating ligand of the heme iron. To our knowledge, this patient is the first adult to have described the cardinal features of a syndrome of aromatase deficiency. Recognition that such defects exist will lead to a better understanding of the role of this enzyme in human development and disease.
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KEYWORD
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