A mutational hot spot in the Prop-1 gene in Russian children with combined pituitary hormone deficiency

• Published in: Pituitary 1998-04, Vol.1 (1), p.45-49
• Main Authors: Fofanova, O V, Takamura, N, Kinoshita, E, Parks, J S, Brown, M R, Peterkova, V A, Evgrafov, O V, Goncharov, N P, Bulatov, A A, Dedov, I I, Yamashita, S
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Child; DNA Mutational Analysis; Female; Genes, Recessive; Homeodomain Proteins - genetics; Human Growth Hormone - deficiency; Humans; Male; Mice; Mutation; Pedigree; Pituitary Hormones - deficiency; Prolactin - deficiency; Russia; Sequence Deletion; Syndrome; Thyrotropin - deficiency
• ISSN: 1386-341X
• DOI: 10.1023/A:1009918924945

Combined pituitary hormone deficiency (CPHD), including growth hormone (GH), prolactin (Prl) and thyroid-stimulating hormone (TSH) in children is now considered a heterogeneous syndrome. Recent findings on expression of mouse pituitary-specific homeodomain factors demonstrate dependence of adenopituitary ontogeny on interactive expression of these factors, suggesting their involvement in etiology of CPHD. Prophet of Pit-1 (Prop-1) gene, a novel pituitary-specific homeodomain factor, was analyzed in 14 Russian children with CPHD, in whom Pit-1 gene was intact. We found a mutational hot spot in three patients from two families in homeodomain part of the second exon of Prop-1 gene. The common 2-base pair deletion (GA296) in the homozygous state resulted in a Serine to Stop codon (S109X) substitution and generated a truncated Prop-1 protein. Parents were phenotypically normal and heterozygous for GA296 deletion, indicating an autosomal recessive inheritance. These results demonstrate a novel type of Prop-1 gene mutation as one of the causes of CPHD in Russian patients.