title: The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient.
abstract: The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland. Patients with POU1F1 mutations show a combined pituitary hormone deficiency with low or absent levels of GH, prolactin, and TSH. Fourteen mutations have been reported in the POU1F1 gene up to now. These genetic lesions can be inherited either in an autosomal dominant or an autosomal recessive mode. We report on the first Italian patient, a girl, affected by combined pituitary hormone deficiency. The patient was found to be positive for congenital hypothyroidism (with low TSH levels) at neonatal screening. Substitutive therapy was started, but subsequent growth was very poor, although psychomotor development was substantially normal. Hospitalized at 10 mo she showed hypotonic crises, growth retardation, delayed bone age, and facial dysmorphism. In addition to congenital hypothyroidism, GH and prolactin deficiencies were found. Mutation DNA analysis of the patient's POU1F1 gene identified the novel Q167K amino acid change at the heterozygous level. The highly conserved Q167 residue is located in the POU-specific domain. No mutation was detected in the other allele. DNA analysis in the proband's parents did not identify this amino acid substitution, suggesting a de novo genetic lesion. From these data it can be hypothesized that the Q167K mutation has a dominant negative effect.
authors.affiliation: Department of Paediatrics, University of Florence, 50132 Florence, Italy. zammarchi@unifi.it
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Giovanni Maria
authors.initials: GM
authors.lastname: Poggi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pasquini
authors.forename: Maria Alice
authors.initials: MA
authors.lastname: Donati
authors.forename: Ivana
authors.initials: I
authors.lastname: Pela
authors.forename: Amelia
authors.initials: A
authors.lastname: Morrone
authors.forename: Enrico
authors.initials: E
authors.lastname: Zammarchi
mesh_terms: D000595:Amino Acid Sequence; D003409:Congenital Hypothyroidism; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007223:Infant; D007558:Italy; D008969:Molecular Sequence Data; D017354:Point Mutation; D011388:Prolactin / Q000172:deficiency*; D016415:Sequence Alignment; D013972:Thyrotropin / Q000172:deficiency*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D019382:Human Growth Hormone; D011388:Prolactin; D013972:Thyrotropin