Variable Phenotypes in Familial Isolated Growth Hormone Deficiency Caused by a G6664A Mutation in the GH-1 Gene
| Autor: | Zvi Zadik, Idit Lavi, Yardena Tenenbaum-Rakover, Ora Hess, Yasir Hujeirat, Michael Wajnrajch, Stavit Allon-Shalev |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Genotype Arginine Endocrinology Diabetes and Metabolism DNA Mutational Analysis Clinical Biochemistry Twins Context (language use) Biology Biochemistry Endocrinology Internal medicine medicine Humans Insulin-Like Growth Factor I Child Aged Aged 80 and over Transition (genetics) Human Growth Hormone Biochemistry (medical) Infant Bone age DNA Middle Aged medicine.disease Obesity Arabs Pedigree Phenotype Child Preschool Jews Mutation Mutation (genetic algorithm) IGHD Female Restriction fragment length polymorphism |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 92:4387-4393 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2007-0684 |
| Popis: | Context: G to A transition at position 6664 (G6664A) in human GH-1 results in the substitution of arginine by histidine at position 183 (R183H) of the GH molecule and causes familial isolated GH deficiency type II (IGHD II). Objectives: The objective of the study was to assess the phenotypegenotype correlation of subjects affected with IGHD II caused by a G6664A mutation in 34 affected members of two large families. Design and Patients: Sixty-six subjects from two core families were included. The G6664A mutation among family members was determined by restriction fragment length polymorphism. Results: Twenty-four of the 52 members from family 1 and 10 of 14 from family 2 carried the same G6664A mutation in a heterozygous state. The affected subjects in family 1 were significantly shorter [2.6 vs. 0.1 SD score (SDS), P 0.0001] and had significantly lower IGF-I serum levels (1.9 vs. 0.5 SDS, P 0.0001), compared with normal-genotypefamilymembers.Theaffectedadultsexhibitedgreat variability in their stature, ranging from 4.5 to 1.0 (mean 2.8 SDS), with five members being of normal height (2 SDS). Twelve children were diagnosed with IGHD. Two affected children had normal peak GH levels, although one of these subsequently demonstrated GH insufficiency (6.5 and 3.7 ng/ml). The affected children from both families exhibited large variability in their height, growth velocity, delay in bone age (chronological age bone age), age at diagnosis, peak GH response, and IGF-I levels. Conclusions: These detailed phenotypic analyses show the variable expressivity of patients bearing a G6664A mutation, reflecting the spectrum of GH deficiency in affected patients, even within families, and the presence of additional genes modifying height determination. Our findings raise a new dilemma in the guidelines for the diagnosis of GH deficiency and the indications for GH therapy. (J Clin Endocrinol Metab 92: 4387–4393, 2007) |
| Databáze: | OpenAIRE |
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