Isolated central hypothyroidism in young siblings as a manifestation of PROP1 deficiency: Clinical impact of whole exome sequencing

Ari J. Wassner, Laurie E. Cohen, Eliana Hechter, Andrew Dauber

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Background/Aims: Central hypothyroidism (CH) in children is rare and may be due to a variety of genetic defects. Most of these defects, but not all, are associated with additional pituitary hormone deficits. In a young child presenting with CH, it is important to determine whether additional pituitary hormone deficiencies are present, but this may be difficult to establish clinically. Methods: We describe the clinical characteristics of two young siblings, aged 6 months and 2 years, presenting with isolated CH. Whole exome sequencing was performed to determine the genetic basis of isolated CH. Results: A homozygous frameshift mutation of PROP1 (296delGA) was identified in both probands. Defects in PROP1 cause progressive deficiency of multiple pituitary hormones. Based on this genetic diagnosis, further clinical testing was performed that demonstrated growth hormone deficiency in one sibling. Conclusions: PROP1 deficiency may present as isolated CH at a very young age. In disorders with multiple potential causative genes, whole exome sequencing may facilitate rapid genetic diagnosis and lead to important changes in clinical management.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalHormone Research in Paediatrics
Volume79
Issue number6
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Central hypothyroidism
  • Gene diagnostics
  • Genetics of endocrinopathies
  • PROP-1
  • Whole exome sequencing

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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