A Deletion of More than 800 kb Is the Most Recurrent Mutation in Chilean Patients with SHOX Gene Defects

作者：Poggi Helena; Vera Alejandra; Avalos Carolina; Lagos Marcela; Mellado Cecilia; Aracena Mariana; Aravena Teresa; Garcia Hernan; Godoy Claudia; Cattani Andreina; Reyes Loreto; Lacourt Patricia; Rumie Hana; Mericq Veronica; Arriaza Marta; Martinez Aguayo Alejandro^*

来源：Hormone Research in Paediatrics, 2015, 84(4): 254-257.

DOI：10.1159/000439109

• SHOX deficiency
• Short stature
• Leri-Weill syndrome
• Langer mesomelic dysplasia

Background: Deletions in the SHOX gene are the most frequent genetic cause of Leri-Weill syndrome and Langer mesomelic dysplasia, which are also present in idiopathic short stature. Aim: To describe the molecular and clinical findings observed in 23 of 45 non-consanguineous Chilean patients with different phenotypes related to SHOX deficiency. Methods: Multiplex ligation-dependent probe amplification was used to detect the deletions; the SHOX coding region and deletion-flanking areas were sequenced to identify point mutations and single-nucleotide polymorphisms (SNPs). Results: The main genetic defects identified in 21 patients consisted of deletions; one of them, a large deletion of >800 kb, was found in 8 patients. Also, a smaller deletion of >350 kb was observed in 4 patients. Although we could not precisely determine the deletion breakpoint, we were able to identify a common haplotype in 7 of the 8 patients with the larger deletion based on 22 informative SNPs. Conclusion: These results suggest that the large deletion-bearing allele has a common ancestor and was either introduced by European immigrants or had originated in our Amerindian population. This study allowed us to identify one recurrent deletion in Chilean patients; also, it contributed to expanding our knowledge about the genetic background of our population.

• 出版日期2015