Combined pituitary hormone deficiency (CPHD) due to a complete PROP1 deletion.
OBJECTIVE
PROP1 mutations are the most common cause of genetic combined pituitary hormone deficiency (CPHD). The aim of this study was to investigate the PROP1 gene in two siblings with CPHD.


METHODS
Pituitary function and imaging assessment and molecular analysis of PROP1.


METHODS
Two siblings, born to consanguineous parents, presented with GH deficiency associated with other pituitary hormone deficiencies (TSH, PRL and gonadotrophins). The male sibling also had an evolving cortisol deficiency.


METHODS
Pituitary size was evaluated by magnetic resonance imaging (MRI). PROP1 gene analysis was performed by polymerase chain reaction (PCR), automatic sequencing and Southern blotting. Amplification of sequence tag sites (STS) and the Q8N6H0 gene flanking PROP1 were performed to define the extension of PROP1 deletion.


RESULTS
MRI revealed a hypoplastic anterior pituitary in the girl at 14 years and pituitary enlargement in the boy at 18 years. The PROP1 gene failed to amplify in both siblings, whereas other genes were amplified. Southern blotting analysis revealed the PROP1 band in the controls and confirmed complete PROP1 deletion in both siblings. The extension of the deletion was 18.4 kb. The region flanking PROP1 contains several Alu core sequences that might have facilitated stem-loop-mediated excision of PROP1.


CONCLUSIONS
We report here a complete deletion of PROP1 in two siblings with CPHD phenotype.
Abrão
M G
MG
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular - LIM/42, Disciplina de Endocrinologia, HCFMUSP, Sao Paulo, Brazil.
Leite
M V
MV
Carvalho
L R
LR
Billerbeck
A E C
AE
Nishi
M Y
MY
Barbosa
A S
AS
Martin
R M
RM
Arnhold
I J P
IJ
Mendonca
B B
BB
D000293:Adolescent; D015139:Blotting, Southern; D003241:Consanguinity; D004393:Dwarfism, Pituitary / Q000235:genetics* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007018:Hypopituitarism / Q000235:genetics* / Q000473:pathology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000473:pathology; D035781:Siblings
D018398:Homeodomain Proteins; C102134:Prophet of Pit-1 protein