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Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging.
- Source :
-
Hormone research [Horm Res] 2003; Vol. 60 (6), pp. 277-83. - Publication Year :
- 2003
-
Abstract
- Background/aims: Many genes encoding pituitary transcription factors involved in the formation of the pituitary gland are identified. Different mutations in these genes have been reported in patients with familial combined pituitary hormone deficiency (CPHD). This study was undertaken to analyze PIT1, PROP1, LHX3, and HESX1 in 12 CPHD patients with abnormal pituitary magnetic resonance imaging (MRI). Since embryonic development of the pituitary requires the coordinated expression of specific transcription factors, we postulated the presence of mutations in PIT1, PROP1, LHX3, and HESX1 genes.<br />Methods: Anterior pituitary function was evaluated. Each gene was PCR amplified exon by exon, and subsequently sequenced.<br />Results: In all cases, MRI examination showed abnormal pituitary gland development featuring ectopic neurohypophysis, hypoplastic anterior lobe, empty sella, and septo-optic dysplasia. Endocrinologically, all patients revealed multiple pituitary hormone deficiency including growth hormone, thyroid stimulating hormone, luteinizing hormone, follicular stimulating hormone and adrenocorticotropin. They were all sporadic cases without a positive family history. None of disease-causing specific mutations were identified in PIT1, PROP1, LHX3, and HESX1 genes of 12 sporadic CPHD patients with abnormal pituitary imaging. However, 2 novel polymorphisms were found in PROP1 gene: IVS1+3 A-->G and 27 T-->C (Ala9Ala) in exon 1. Their allele frequencies in patients and normal controls were not statistically different. Overall, allele frequencies of these polymorphisms were as follows: for the IVS1+3 A-->G polymorphism, the allele frequency of A was 54%, and 46% for G, with 58% of an A/G heterozygosity. For the 27 T-->C (Ala9Ala) polymorphism, the allele frequency of T was 46%, and 54% for G, with 42% of a T/C heterozygosity.<br />Conclusions: Mutations of PIT1, PROP1, LHX3, and HESX1 genes are very rare in sporadic CPHD patients with abnormal pituitary MRI.<br /> (Copyright 2003 S. Karger AG, Basel)
- Subjects :
- Adolescent
Body Height genetics
Child
Child, Preschool
Exons genetics
Female
Gene Amplification
Gene Frequency
Humans
Infant
Male
Pituitary Gland, Anterior pathology
Pituitary Gland, Anterior physiopathology
Pituitary Gland, Posterior abnormalities
Pituitary Gland, Posterior pathology
Pituitary Hormones blood
Polymerase Chain Reaction methods
Polymorphism, Genetic
Sequence Analysis, DNA methods
Magnetic Resonance Imaging methods
Pituitary Gland, Anterior ultrastructure
Pituitary Gland, Posterior ultrastructure
Pituitary Hormones deficiency
Pituitary Hormones genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0301-0163
- Volume :
- 60
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Hormone research
- Publication Type :
- Academic Journal
- Accession number :
- 14646405
- Full Text :
- https://doi.org/10.1159/000074245