Session: OR20-Genetics of Growth
Bench to Bedside
Room 122 (Moscone Center)
Objective and hypothesis: To test the hypothesis that STAT5B haploinsufficiency could cause an intermediate phenotype between patients with homozygous mutations and controls.
Methods: Direct relatives of two patients homozygous for the p.L142fsX161 (c.424_427del) STAT5B mutation were evaluated (1). We compared clinical and laboratory characteristics between relatives heterozygous for the STAT5Bmutation and non-carriers. In this way the differences related to different genetic backgrounds could be minimized.
Results: We investigated a total of 32 direct relatives of the index patient. Fourteen of them carry the heterozygous c.424_427del STAT5B mutation. Individuals carrying STAT5B mutation and the ones homozygous for the wild type (WT) allele have similar gender distribution and ages. However, individuals heterozygous for STAT5B mutation (height SDS = -0.9 ± 0.6) were significantly shorter than WT ones (height SDS = 0.0 ± 1.1; p = 0.012; 95% confidence interval: -1.6 to -0.2). Additionally, IGF-1 levels had a tendency to be lower in relatives carrying the mutation (IGF-1 SDS = -0.5 ± 1.1 vs. +0.2 ± 1.1, p = 0.086). There were no differences between the two groups of relatives regarding basal GH, PRL, IGFBP-3, glucose, insulin, C-peptide levels, serum immunoglobulins. A lower lymphocyte concentration was observed in relatives heterozygous for STAT5B mutation (1738 ± 368 per ml vs 2218 ± 690 per ml in WT; p = 0.026). Interestingly, two relatives carrying STAT5B mutation were diagnosed with “idiopathic” pulmonary fibrosis.
Conclusions: Individuals heterozygous for the studied STAT5B mutation are shorter than their non-carrier relatives, although in the normal height range. In the same direction, IGF-1 SDS was lower in heterozygous individuals, although without reaching significance. A tendency toward more respiratory allergy and a decrease of serum lymphocytes were also observed in carriers. These results suggest a mild phenotype in individuals heterozygous for STAT5B mutations, but it is necessary to expand the number of studied relatives in this and other families to confirm the present findings.
Nothing to Disclose: RDCS, CAT, PP, JC, IJA, AALJ
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