Genetic screening of a Dutch population with isolated GH deficiency (IGHD).
Clin Endocrinol (Oxf)
; 70(5): 742-50, 2009 May.
Article
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| MEDLINE
| ID: mdl-18785993
ABSTRACT
OBJECTIVE:
Five per cent to 30% of cases of idiopathic isolated GH deficiency (IGHD) have first-degree relatives with short stature, which is suggestive of a genetic aetiology. The HYPOPIT study aimed to obtain an overall picture of gene encoding pituitary GH (GH1) and gene encoding GH releasing hormone-receptor (GHRHR) defects in a Dutch IGHD cohort and to relate them with clinical parameters. DESIGN, PATIENTS AND MEASUREMENTS Genetic analysis was performed of exons and exon-intron boundaries of GH1 and GHRHR in 89 Caucasian IGHD patients from 81 families, using denaturing high-performance liquid chromatography (dHPLC), DNA sequencing and multiplex ligation-dependent probe amplification. In addition, we performed functional studies on novel identified GH1 exonic variants.RESULTS:
Five different heterozygous GH1 mutations were present in 5 out of 81 participating families (6.1%), whereas no mutations in GHRHR were found. Patients with IGF-I SDS < -4.0 and peak GH levels < 5.7 mU/l had a mutation frequency of 40%, in contrast to 6.8% in patients with only one criterion, and 0.0% in patients with none of these criteria (P = 0.00007). Five new GH1 and two GHRHR variants were also identified; two of them (GH1 F92L and D153H) caused a marked reduction of GH secretion in vitro.CONCLUSION:
GH1 and GHRHR mutations are rare in Caucasian Dutch IGHD patients, which suggests the involvement of other genetic determinants in the aetiology of IGHD. IGF-I < -4.0 and peak GH levels < 5.7 mU/l are strong predictors of GH1 mutations in the studied population.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Hormona de Crecimiento Humana
Tipo de estudio:
Diagnostic_studies
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
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Screening_studies
Límite:
Animals
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Child, preschool
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Female
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Humans
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Infant
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Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Clin Endocrinol (Oxf)
Año:
2009
Tipo del documento:
Article
País de afiliación:
Países Bajos