Idioma:

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

CONTE, F. A ; GRUMBACH, M. M ; ITO, Y ; FISHER, C. R ; SIMPSON, E. R

Journal of Clinical Endocrinology and Metabolism, 1994-06, Vol.78 (6), p.1287-1292 [Periódico revisado por pares]

Bethesda, MD: Endocrine Society

Sem texto completo

Citações Citado por

Enviar para

Título:
A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)
Autor: CONTE, F. A ; GRUMBACH, M. M ; ITO, Y ; FISHER, C. R ; SIMPSON, E. R
Assuntos: 17-alpha-Hydroxypregnenolone - blood ; 17-alpha-Hydroxyprogesterone ; Adolescent ; Adrenocorticotropic Hormone ; Androgens - blood ; Aromatase - genetics ; AROMATIZATION ; Biological and medical sciences ; BIOLOGY AND MEDICINE, BASIC STUDIES ; Cortodoxone - blood ; Disorders of Sex Development - enzymology ; Disorders of Sex Development - genetics ; Disorders of Sex Development - physiopathology ; ENDOCRINE DISEASES ; ENZYMES ; Estradiol - blood ; Female ; Female genital diseases ; FEMALES ; Follicle Stimulating Hormone - blood ; Follicle Stimulating Hormone - secretion ; GENE MUTATIONS ; Gonadotropin-Releasing Hormone ; Gynecology. Andrology. Obstetrics ; Humans ; Hydroxyprogesterones - blood ; Hypogonadism - enzymology ; Hypogonadism - genetics ; Hypogonadism - physiopathology ; Luteinizing Hormone - blood ; Luteinizing Hormone - secretion ; Medical sciences ; Non tumoral diseases ; Ovary - pathology ; Point Mutation ; Polycystic Ovary Syndrome - enzymology ; Polycystic Ovary Syndrome - genetics ; Polycystic Ovary Syndrome - physiopathology ; STEROIDS ; Syndrome
É parte de: Journal of Clinical Endocrinology and Metabolism, 1994-06, Vol.78 (6), p.1287-1292
Notas: ObjectType-Case Study-3
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-4
content type line 23
ObjectType-Report-2
Descrição: We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.
Editor: Bethesda, MD: Endocrine Society
Idioma: Inglês

Links

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom)

CONTE, F. A ; GRUMBACH, M. M ; ITO, Y ; FISHER, C. R ; SIMPSON, E. R

Bethesda, MD: Endocrine Society

Buscando em bases de dados remotas. Favor aguardar.