No abstract

We report here a complete deletion of PROP1 in two siblings with CPHD phenotype.

Spontaneous mouse mutants greatly contributed to our initial understanding of CPHD genetics. The Snell and Jackson mice had GH, prolactin and TSH deficiencies. In the early '90s, mutations in Pit1, which encodes pituitary-specific transcription factor-1, were described in these animals (7,8). This finding quickly led to the detection of mutations in the human homologue gene POU1F1 (previously known as PIT1) with a similar phenotype (9,10). The Ames dwarf mouse, another spontaneous mutant mouse with a similar phenotype, but without mutations in Pit1, had the genetic cause established a little while later: mutations in a paired-like homeodomain transcription factor termed 'Prophet of Pit1' (Prop1) (11). The Ames dwarf phenotype resulted from an apparent failure of initial determination of the Pit1 lineage, required for

PROP1 mutations are a prevalent cause of congenital CPHD with OPP, and therefore, PROP1 sequencing must be the first step of molecular investigation in patients with CPHD and OPP, especially in populations with a high frequency of PROP1 mutations. In the absence of mutations, massively parallel sequencing is a promising approach. The high prevalence and diversity of PROP1 mutations is associated with the ethnic background of this cohort.