Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT)

Area of Science:

• Genetics
• Endocrinology
• Pediatrics

Background:

• Combined pituitary hormone deficiency (CPHD) is a disorder of the anterior pituitary gland often leading to growth retardation.
• PROP1 gene mutations are a common cause of CPHD, especially in certain geographic regions, but are less frequently reported in Japan.

Observation:

• Two sisters presented with proportional short stature starting around age two.
• Magnetic resonance imaging (MRI) showed only slight pituitary hypoplasia.
• Hormone analysis revealed deficiencies in growth hormone (GH), thyroid stimulating hormone, prolactin, and gonadotropins, with adequate adrenocorticotropin secretion.

Findings:

• Genetic analysis identified a novel, familial, autosomal recessive PROP1 gene mutation (467insT) in the sisters.
• This insertion mutation is located in the transcription-activating region of the PROP1 gene.
• The mutation results in a non-functional PROP1 protein lacking its transcription activation domain.

Implications:

• The identified mutation provides a genetic explanation for severe GH deficiency and subsequent growth retardation in the affected siblings.
• This case expands the known spectrum of PROP1 mutations associated with CPHD.
• Understanding these mutations is crucial for accurate diagnosis and potential therapeutic strategies in pediatric growth disorders.