A novel PROP1 gene mutation (157delA) in Japanese siblings with combined anterior pituitary hormone deficiency

OBJECTIVE The majority of cases of combined anterior pituitary hormone deficiency (CPHD) reported in Japanese patients have PIT1 abnormality. This study describes for the first time a homozygous mutation of the PROP1 gene in two Japanese siblings with CPHD born to consanguineous parents. PATIENTS Two siblings were growth retarded at 3 years of age and developed hypothyroidism. Pituitary function tests showed combined deficiency of GH, TSH, PRL and gonadotrophins. The size of their pituitary glands decreased with age, as demonstrated by magnetic resonance imaging (MRI). RESULTS The PROP1 gene was analysed by polymerase chain reaction (PCR) followed by direct sequencing. Both children were homozygous for a novel single base deletion at codon 53 (157delA), while their parents were heterozygous. This mutation, if translated, predicts the production of a protein lacking the paired-like homeodomain required for DNA binding, suggesting that the mutation was the direct cause of CPHD in these patients. CONCLUSIONS 157delA is the first reported Japanese PROP1 gene mutation. In Japan, PROP1 abnormality appears to be a less frequent cause of CPHD than does PIT1 abnormality, whereas PROP1 abnormality predominates in CPHD patients of Caucasian and European origin.