Congenital hypopituitarism in familial Turner syndrome cases caused by a highly prevalent PROP1 gene mutation in Tunisia

Background: Turner syndrome (TS) is a genetic disorder found only in females who are completely or partially missing an X chromosome. It is rarely inherited from parent to offspring and is not reported to be associated with any causal gene. In addition, familial forms are less frequent than sporadic ones. A Tunisian family with four girls affected by TS showed an unusual association with congenital hypopituitarism among three of them. Objectives: Conduct a genetic investigation by exploring the PROP1 gene genomic sequence to identify a possible causal variant explaining the simultaneous presence of the TS and the congenital hypopituitarism in the family. Methods: The coding regions of the gene and their flanking introns are Sanger sequenced among four sisters and their mother and compared to the reference sequences. Results: Sequences analysis showed the presence of the PROP1 gene mutation p.Arg73Cys (rs121917843), the most frequent Maghrebian defect responsible for non-syndromic combined pituitary hormone deficiency. The girls with both TS and congenital hypopituitarism were homozygous. However, the sister who was affected by TS only and their healthy mother were heterozygous. Conclusion: Our findings showed that the uncommon association between TS and congenital hypopituitarism is a random event caused by the high frequency of the PROP1 p.Arg73Cys mutation and the high level of consanguinity in the Tunisian population.