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Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency

O Fofanova1, N Takamura, E Kinoshita

  • 1Endocrinology Research Center, Moscow, Russia.

The Journal of Clinical Endocrinology and Metabolism
|July 14, 1998
PubMed

Insights

Mutations in the prophet of Pit-1 gene (PROP1) cause combined pituitary hormone deficiency (CPHD). Two common deletions in PROP1, 149delGA and 296delGA, were found to cause CPHD in Russian children, often in compound heterozygosity.

Area of Science:

  • Genetics
  • Endocrinology
  • Molecular Biology

Background:

  • Prophet of Pit-1 (PROP1) gene mutations are a known cause of combined pituitary hormone deficiency (CPHD).
  • Previous studies identified homozygosity for the 296delGA deletion in PROP1 causing CPHD in Russian families.
  • CPHD is characterized by deficiencies in growth hormone, prolactin, thyroid-stimulating hormone, and gonadotropins.

Purpose of the Study:

  • To identify novel mutations and mutational hotspots in the PROP1 gene associated with CPHD.
  • To investigate the frequency of specific PROP1 mutations in Russian children diagnosed with CPHD.
  • To determine the role of compound heterozygosity for PROP1 deletions in the etiology of CPHD.

Main Methods:

  • Genetic analysis of PROP1 in a cohort of Russian children with CPHD.
  • Sequencing of exon 2 of the PROP1 gene to detect deletions.
  • Analysis of mutation patterns, including homozygosity and compound heterozygosity.

Main Results:

  • A second mutational hotspot in exon 2 of PROP1, the 149delGA deletion, was identified.
  • This deletion results in a frameshift and a premature stop codon (S109X), leading to a truncated protein.
  • Compound heterozygosity for the two common deletions (149delGA/296delGA) was found in 36% of CPHD children studied.
  • This compound heterozygous state was detected in 5 out of 14 CPHD children from 4 families.

Conclusions:

  • The 149delGA deletion represents a second common mutational hotspot in the PROP1 gene.
  • Compound heterozygosity for the 149delGA and 296delGA deletions is a significant cause of CPHD in Russian children.
  • This finding highlights the importance of investigating compound heterozygosity for common deletions in PROP1-related CPHD.

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