Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population.
BACKGROUND
The aim of our study was to describe a large population with anomalies involving the SHOX region, responsible for idiopathic short stature and Léri-Weill dyschondrosteosis (LWD), and to identify a possible genotype/phenotype correlation.


METHODS
We performed a retrospective multicenter study on French subjects with a SHOX region anomaly diagnosed by multiplex ligation-dependent probe amplification or Sanger sequencing. Phenotypes were collected in each of the 7 genetic laboratories practicing this technique for SHOX analysis.


RESULTS
Among 205 index cases and 100 related cases, 91.3% had LWD. For index cases, median age at evaluation was 11.7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients. Duplications and point mutations/indels affected 8 and 18% of the population, respectively. Genotype-phenotype correlation showed that deletions were more frequently associated with Madelung deformity and mesomelic shortening in girls, as well as with presence of radiologic anomalies, than duplications.


CONCLUSIONS
Our results highlight genotype-phenotype relationships in the French population with a SHOX defect and provide new information showing that clinical expression is milder in cases of duplication compared to deletions.
Department of Pediatrics and Medical Genetics, Brabois Hospital, Vandoeuvre-lès-Nancy, France.
Julie
J
Auger
Amandine
A
Baptiste
Imane
I
Benabbad
Gaëlle
G
Thierry
Jean-Marc
JM
Costa
Mélanie
M
Amouyal
Marie-Laure
ML
Kottler
Bruno
B
Leheup
Renaud
R
Touraine
Sébastien
S
Schmitt
Marine
M
Lebrun
Valérie
V
Cormier Daire
Jean-Paul
JP
Bonnefont
Nicolas
N
de Roux
Caroline
C
Elie
Myriam
M
Rosilio
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D005602:France; D005838:Genotype; D006130:Growth Disorders / Q000235:genetics* / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D044463:Receptor, PAR-1 / Q000235:genetics; D000074122:Short Stature Homeobox Protein
D018398:Homeodomain Proteins; D044463:Receptor, PAR-1; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein