| Autor: |
Hisado-Oliva, Alfonso, Garre-Vázquez, Ana I., Santaolalla-Caballero, Fabiola, Belinchón, Alberta, Barreda-Bonis, Ana C., Vasques, Gabriela A., Ramirez, Joaquin, Luzuriaga, Cristina, Carlone, Gianni, González-Casado, Isabel, Benito-Sanz, Sara, Jorge, Alexander A., Campos-Barros, Angel, Heath, Karen E. |
| Zdroj: |
The Journal of Clinical Endocrinology & Metabolism; August 2015, Vol. 100 Issue: 8 pE1133-E1142, 10p |
| Abstrakt: |
Context:SHOXmutations have been detected in approximately 70% of Léri-Weill dyschondrosteosis (LWD) and approximately 2.5% of idiopathic short stature (ISS) cases, suggesting the implication of other genes or loci. The recent identification of NPR2mutations in ISS suggested that NPR2mutations may also be involved in disproportionate short stature.Objective:The objective of the study was to investigate whether NPR2mutations can account for a proportion of the cases referred for LWD and ISS in whom no SHOXmutation was detected.Patients and Methods:We undertook NPR2mutation screening in 173 individuals referred for suspected LWD and 95 for ISS, with no known defect in SHOXor its enhancers. Intracellular localization and natriuretic peptide precursor C-dependent guanylate cyclase activity were determined for the identified NPR2variants.Results:Eight NPR2variants were identified in nine individuals, seven referred for suspected LWD and two for ISS. Six were demonstrated to affect NPR-B cell trafficking and/or its ability to synthesize cyclic GMP (cGMP) under response to natriuretic peptide precursor C/brain natriuretic peptide stimulation. All pathogenic mutations were detected in the suspected LWD referral group (∼3%). Interestingly, one of these patients is currently being treated with recombinant human GH and in contrast to previous reports is showing a positive response to the treatment.Conclusions:NPR2mutations account for approximately 3% of patients with disproportionate short stature and/or clinical or radiographic indicators of SHOX deficiency and in whom no SHOXdefect has been identified. However, no patient has yet presented with Madelung deformity. Thus, NPR2should be screened in the SHOX-negative LWD referrals. |
| Databáze: |
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