Phenotype: Pituitary Hormone Deficiency

Name of the : PROP1 (PROP paired-like 1)

Location of the gene: 5q35.3 ( 5 arm: long (q); region: 35.3) http://www.genecards.org/cgi-bin/carddisp.pl?gene=prop1

Profile of gene Expression and protei n location

This gene is expressed mainly in embryonic pituitary (hypophysis) and in pituitary tumors. The subcellular location of the is in nucleus.

Protein Name Homeobox protein prophet of Pit-1 Accession Uniprot: O75360 Length: 226 amino acids Molecular Weight: 24984 Da 3D Structure: not found

Function and Description The PROP1 gene provides instructions for making a protein that has DNA-binding and transcriptional activation ability, so helps control the activity of many other . This protein is found only in the pituitary gland, which is located at the base of the brain. The pituitary gland releases hormones needed for growth, reproduction, and other critical body functions.

Mutations and Pathologies: OMIM ACCESS: 601538

At least 25 mutations in the PROP1 gene have been found to cause combined pituitary hormone deficiency. The most common mutation deletes two nucleotides in the PROP1 gene (301-302delAG). This deletion leads to the production of an abnormally short protein that cannot function properly. The shortened protein is less able to control the activity of other genes, which reduces pituitary cell differentiation and prevents the release of hormones like growth hormone (GH); thyroid-stimulating hormone (TSH); the two gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH); prolactin (PrL); and occasionally adrenocorticotropic hormone (ACTH) from the gland.

A lack of these hormones may affect the development of many parts of the body. The first signs of this condition include a failure to grow at the expected rate and short stature that usually becomes apparent in early childhood. Affected individuals can have absent or delayed and incomplete secondary sexual development with infertility.

Congenital hypopituitarism is due to mutations of several genes encoding pituitary transcription factors: PROP1, POU1F1,HEX1 and LHX4, phenotype varies with the factor involved.

Frequency and Transmission

The prevalence of combined pituitary hormone deficiency is estimated to be 1 in 8,000 individuals worldwide. Type of transmission varies with the factor and the mutation involved. PROP1-related combined pituitary hormone deficiency is inherited in an autosomal recessive manner. Heterozygotes are asymptomatic.

Diagnosis and Clinical Treatment

Actually the only way to treat this condition is the a hormone therapy. https://www.ncbi.nlm.nih.gov/books/NBK279161/

! ! A girl with a PROP1 gene defect (150delA/301delGA) at her first; second; fourth birthdays. She started on GH and thyroxine therapy at 6.7 years of age. Last photograph shows her current status at 14 years of age. Typical facial appearance of growth hormone deficiency (frontal bossing, flat nasal bridge) may be noticed during early childhood; however, the typical phenotype disappeared later while under GH therapy. Curiosity Messi was diagnosed GHD (Growth Hormone Deficiency) at the age of 11 is a disorder caused due to the malfunction of the pituitary gland. This gland is responsible for the production of growth hormones, which allow children to grow and keep a check on bone density, muscle elasticity and the distribution of body fat in adults. The causes of this disorder may be different: genes mutation, infections, brain tumour, injuries or radiation therapy. The administration of synthetic GH allowed Messi to achieve success.