Article ; Online: Impact of heterozygosity for acid-labile subunit (IGFALS) gene mutations on stature: results from the international acid-labile subunit consortium.
The Journal of clinical endocrinology and metabolism
2010 Volume 95, Issue 9, Page(s) 4184–4191
Abstract: Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown.: Objective: The study evaluates the impact of heterozygous ... ...
| Abstract | Context: To date, 16 IGFALS mutations in 21 patients with acid-labile subunit (ALS) deficiency have been reported. The impact of heterozygosity for IGFALS mutations on growth is unknown. Objective: The study evaluates the impact of heterozygous expression of IGFALS mutations on phenotype based on data collected by the International ALS Consortium. Subjects/methods: Patient information was derived from the IGFALS Registry, which includes patients with IGFALS mutations and family members who were either heterozygous carriers or homozygous wild-type. Within each family, the effect of IGFALS mutations on stature was analyzed as follows: 1) effect of two mutant alleles (2ALS) vs. wild-type (WT); 2) effect of two mutant alleles vs. one mutant allele (1ALS); and 3) effect of one mutant allele vs. wild-type. The differences in height sd score (HtSDS) were then pooled and evaluated. Results: Mean HtSDS in 2ALS was -2.31 +/- 0.87 (less than -2 SDS in 62%); in 1ALS, -0.83 +/- 1.34 (less than -2 SDS in 26%); and in WT, -1.02 +/- 1.04 (less than -2 SDS in 12.5%). When analyses were performed within individual families and pooled, the difference in mean HtSDS between 2ALS and WT was -1.93 +/- 0.79; between 1ALS and WT, -0.90 +/- 1.53; and between 2ALS and 1ALS, -1.48 +/- 0.83. Conclusions: Heterozygosity for IGFALS mutations results in approximately 1.0 SD height loss in comparison with wild type, whereas homozygosity or compound heterozygosity gives a further loss of 1.0 to 1.5 SD, suggestive of a gene-dose effect. Further studies involving a larger cohort are needed to evaluate the impact of heterozygous IGFALS mutations not only on auxology, but also on other aspects of the GH/IGF system. |
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| MeSH term(s) | Adolescent ; Adult ; Body Height/genetics ; Carrier Proteins/genetics ; Case-Control Studies ; Child ; Child, Preschool ; Consensus Development Conferences as Topic ; Family ; Female ; Glycoproteins/genetics ; Growth Disorders/genetics ; Heterozygote ; Humans ; International Cooperation ; Loss of Heterozygosity/genetics ; Loss of Heterozygosity/physiology ; Male ; Models, Biological ; Mutation/physiology ; Young Adult | |||||
| Chemical Substances | Carrier Proteins ; Glycoproteins ; insulin-like growth factor binding protein, acid labile subunit | |||||
| Language | English | |||||
| Publishing date | 2010-09 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 3029-6 | |||||
| ISSN | 1945-7197 ; 0021-972X | |||||
| ISSN (online) | 1945-7197 | |||||
| ISSN | 0021-972X | |||||
| DOI | 10.1210/jc.2010-0489 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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