Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1.

Details

Serval ID
serval:BIB_B69F35BCFD4A
Type
Article: article from journal or magazin.
Collection
Publications
Title
Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1.
Journal
The Journal of clinical endocrinology and metabolism
Author(s)
Osorio M.G., Kopp P. (co-first), Marui S., Latronico A.C., Mendonca B.B., Arnhold I.J.
ISSN
0021-972X (Print)
ISSN-L
0021-972X
Publication state
Published
Issued date
08/2000
Peer-reviewed
Oui
Volume
85
Number
8
Pages
2779-2785
Language
english
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
Publication Status: ppublish
Abstract
Mutations in the pituitary-specific paired-like homeodomain transcription factor, PROP-1, result in combined pituitary hormone deficiency. We studied a Brazilian girl, offspring of first cousins, who presented with short stature and deficiencies of GH, TSH, PRL, LH, and FSH. Her cortisol response to hypoglycemia was determined at age 4.9, 10.7, and 14.1 yr and remained normal. Magnetic resonance imaging at the age of 9 yr revealed an anterior pituitary lobe of diminished height (3 mm; normal, 4.5 +/- 0.6), but radiography revealed a sella turcica volume above the normal mean. Direct sequencing of the PROP-1 gene revealed homozygosity for a novel 263T>C transition that results in the replacement of a highly conserved phenylalanine by serine at codon 88 (F88S). F88 constitutes the hydrophobic core of the first helix of the homeodomain of PROP-1, and the substitution by the polar residue serine is expected to alter the secondary structure and impair binding of the mutated PROP-1 to DNA target sequences. The F88S mutation (which corresponds to murine F85S) was introduced into the murine Prop-1 complementary DNA and its consequences on DNA binding and trans-activation were assessed in vitro. In contrast to wild-type Prop-1, the F88S mutant showed no significant DNA binding to a PRDQ9 Prop-1 response element in gel shift assays. Transcriptional activation of a luciferase reporter gene containing a PRDQ9 site upstream of a simian virus 40 promoter was reduced to approximately 34% compared with that of wild-type Prop-1 in transiently transfected TSA-201 human embryonic kidney cells. The F88S mutation further expands the repertoire of mutations in PROP-1.
Keywords
Amino Acid Sequence, Amino Acid Substitution, Base Sequence, Consanguinity, Conserved Sequence, Female, Homeodomain Proteins/genetics, Humans, Hypopituitarism/drug therapy, Hypopituitarism/genetics, Hypopituitarism/physiopathology, Infant, Male, Phenylalanine, Pituitary Gland/diagnostic imaging, Pituitary Hormones/deficiency, Point Mutation, Radiography, Serine
Pubmed
Web of science
Open Access
Yes
Create date
30/12/2020 15:10
Last modification date
31/12/2020 6:26
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