Abstract |
We report on two German sisters with deficiency in the 17alpha- hydroxylase/ 17,20-lyase enzyme corresponding to typical hormone profile. A paternal nonsense mutation R388X in exon 7 and a maternal missense mutation P428L in exon 8 of the CYP17 gene have been identified in both girls. Residual in vitro 17alpha-hydroxylase activity for the conversion of [3H]-Preg to [3H]-17OH-Preg has been detected in transfected 293-cells expressing P428L mutant enzyme; however, no 17,20-lyase activity was observed converting [3H]-17OH-Preg into [3H]- DHEA. The 46,XX-sister spontaneously entered puberty. The 46,XY-sister with a predicted adult height of 203 cm was treated with a high dose of conjugated estrogens and resulted with a final height of 186.9 cm. The present data suggest that compound heterozygous 46,XX females bearing a P428L allele may develop spontaneous onset of puberty. Furthermore, in 46,XY females with tall stature, treatment with conjugated estrogens may lead to a significant reduction of their predicted adult height.
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Authors | Karl Otfried Schwab, Anne-Marie Moisan, Janos Homoki, Michael Peter, Jacques Simard |
Journal | Journal of pediatric endocrinology & metabolism : JPEM
(J Pediatr Endocrinol Metab)
Vol. 18
Issue 4
Pg. 403-11
(Apr 2005)
ISSN: 0334-018X [Print] Germany |
PMID | 15844475
(Publication Type: Case Reports, Journal Article)
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Chemical References |
- Codon, Nonsense
- Estrogens
- Estrogens, Conjugated (USP)
- Arginine
- Proline
- Steroid 17-alpha-Hydroxylase
- Leucine
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Topics |
- Adolescent
- Adrenal Hyperplasia, Congenital
(complications, genetics)
- Adult
- Arginine
- Body Height
- Codon, Nonsense
- Disorders of Sex Development
(complications, etiology, therapy)
- Estrogens
(therapeutic use)
- Estrogens, Conjugated (USP)
(therapeutic use)
- Female
- Growth Disorders
(complications, drug therapy, etiology)
- Heterozygote
- Humans
- Leucine
- Mutation
- Mutation, Missense
- Orchiectomy
- Proline
- Puberty
- Steroid 17-alpha-Hydroxylase
(genetics)
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