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Pituitary dwarfism in the R271W Pit-1 gene mutation
D Aarskog1, H G Eiken, R Bjerknes
1Barneklinikken, Bergen, Norway.
European Journal of Pediatrics
|December 10, 1997
Summary
A Pit-1 gene mutation (R271W) caused severe growth deficiency in a child by affecting pituitary hormone production. This specific mutation is a "hot spot," and a new assay can detect it in patients with suspected growth hormone defects.
Area of Science:
- Genetics
- Endocrinology
- Molecular Biology
Background:
- The Pit-1 gene is crucial for anterior pituitary development and regulating PRL, GH, and TSH genes.
- Pit-1 is a POU-domain transcription factor with DNA-binding domains essential for gene regulation.
- Mutations in Pit-1 can lead to pituitary hypoplasia and deficiencies in growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH).
Observation:
- A 3-month-old girl presented with severe, congenital growth deficiency.
- Genetic analysis revealed a specific Pit-1 gene mutation (R271W) in exon 6, altering the POU homeodomain.
- The patient exhibited characteristic facial features, pituitary hypoplasia, and deficiencies in GH, PRL, and TSH, with altered thyroid hormone conversion.
Findings:
- The R271W mutation in the Pit-1 gene was identified as the cause of the patient's endocrine and growth abnormalities.
- Thyroid function tests suggested increased conversion of T4 to T3, potentially linked to the Pit-1 mutation.
- Treatment with GH and T4 led to significant catch-up growth over five years.
Implications:
- Codon 271 of exon 6 in the Pit-1 gene appears to be a mutation 'hot spot,' as evidenced by this case and previous reports.
- A newly developed amplification-created-restriction-site (ACRS) assay allows for rapid and simple detection of the R271W mutation.
- This assay can aid in diagnosing rare genetic defects affecting growth hormone production, facilitating timely intervention.