We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Variable Phenotypes in Familial Isolated Growth Hormone Deficiency Caused by a G6664A Mutation in the GH-1 Gene.
- Authors
Hess, Ora; Hujeirat, Yasir; Wajnrajch, Michael P.; Allon-Shalev, Stavit; Zadik, Zvi; Lavi, Idit; Tenenbaum-Rakover, Yardena
- Abstract
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 phenotype-genotype 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-genotype family members. The affected adults exhibited great 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
- Publication
Journal of Clinical Endocrinology & Metabolism, 2007, Vol 92, Issue 11, p4387
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2007-0684