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


OBJECTIVE
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.


CONCLUSIONS
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.
Molecular Biology Laboratory, Clinical Laboratory Department, Pontificia Universidad Catx00F3;lica de Chile, Santiago, Chile.
Helena
H
Poggi
Alejandra
A
Vera
Carolina
C
Avalos
Marcela
M
Lagos
Cecilia
C
Mellado
Mariana
M
Aracena
Teresa
T
Aravena
Hernan
H
Garcia
Claudia
C
Godoy
Andreina
A
Cattani
Loreto
L
Reyes
Patricia
P
Lacourt
Hana
H
Rumie
Veronica
V
Mericq
Marta
M
Arriaza
Alejandro
A
Martinez-Aguayo
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002677:Chile; D005260:Female; D017353:Gene Deletion; D006130:Growth Disorders / Q000235:genetics*; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D010641:Phenotype; D000074122:Short Stature Homeobox Protein; D055815:Young Adult
D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein