Abstract
17-OH and 17,20 lyase activities are mediated by cytochrome P450cl7. 17-OH deficiency is rare and only a few cases have been investigated at a molecular genetic level. A 14 y. o. female from rural Thailand was seen by one of us (PM) for fever and muscle weakness for 2 days. Birth and development were unremarkable. Findings included BP 170/120, pre-pubertal breasts, genitalia and axillae and symmetric muscle weakness. Laboratory findings included: Na 149, K 2.1, Cl 100, CO2 30, BUN 6, cortisol 1.0 μg/dl, LH 94 mIU/ml, FSH 99 mIU/L, undetectable aldosterone, testosterone and estraidiol and 46XX karyotype. Ultrasonography showed a prepubertal uterus with normal adrenals and kidneys. A 4-day IM ACTH test showed undetectable 24 h pregnenetriol, 0.9→0.4 mg/24 h pregnenediol, 1.4→3.0 mg/24 h 17KS and 7.6→8.0 mg/24 h 17OHCS. To prove the diagnosis of 17-OH deficiency, the patient's P450cl7 gene was amplified and sequenced by our PCR tactic (Lin et al J Biol Chem 266:15992, 1991). All sequencing was normal except for a 9 bp deletion in exon 8 that deletes the codons for residues 487-489 of P450c17. This deletion creates a BclI site (underlined) in the mutant allele that is absent in the normal, permitting the distinction between homo- and heterozygosity. PCR followed by BelI digestion showed the patient's lesion was homozygous, while the mother and two of three siblings were heterozygous, showing proper Mendelian segregation. This is the first report of this genetic lesion in 17-OH deficiency and the first report of any lesion in a Southeast Asian population.
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Fardella, C., Zhang, L., Mahachoklertwattana, P. et al. HOMOZYGOUS DELETION OF AMINO ACIDS 487–489 IN P450c17 CAUSES SEVERE 17α-HYDROXYLASE (17-OH) DEFICIENCY. Pediatr Res 33 (Suppl 5), S23 (1993). https://doi.org/10.1203/00006450-199305001-00121
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DOI: https://doi.org/10.1203/00006450-199305001-00121