SHOX mutations in idiopathic short stature and Leri-Weill dyschondrosteosis: frequency and phenotypic variability.
Clin Endocrinol (Oxf)
; 66(1): 130-5, 2007 Jan.
Article
in En
| MEDLINE
| ID: mdl-17201812
ABSTRACT
OBJECTIVE:
The frequency of SHOX mutations in children with idiopathic short stature (ISS) has been found to be variable. We analysed the SHOX gene in children with ISS and Leri-Weill dyschondrosteosis (LWD) and evaluated the phenotypic variability in patients harbouring SHOX mutations. PATIENTS Sixty-three ISS, nine LWD children and 21 affected relatives.METHODS:
SHOX gene deletion was evaluated by fluorescence in situ hybridization (FISH), Southern blotting and segregation study of polymorphic marker. Point mutations were assessed by direct DNA sequencing.RESULTS:
None of the ISS patients presented SHOX deletions, but two (3.2%) presented heterozygous point mutations, including the novel R147H mutation. However, when ISS patients were selected by sitting height height ratio (SH/H) for age > 2 SD, mutation frequency detection increased to 22%. Eight (89%) LWD patients had SHOX deletions, but none had point mutations. Analysis of the other relatives in the families carrying SHOX mutations identified 14 children and 17 adult patients. A broad phenotypic variability was observed in all families regarding short stature severity and Madelung deformities. However, the presence of disproportional height, assessed by SH/H, was observed in all children and 82% of adult patients, being the most common feature in our patients with SHOX mutations.CONCLUSION:
Patients with SHOX mutations present a broad phenotypic variability. SHOX mutations are very frequent in LWD (89%), in opposition to ISS (3.2%) in our cohort. The use of SH/H SDS as a selection criterion increases the frequency of SHOX mutation detection to 22% and should be used for selecting ISS children to undergo SHOX mutation molecular studies.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Osteochondrodysplasias
/
Genes, Homeobox
/
Point Mutation
/
Homeodomain Proteins
/
Growth Disorders
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Clin Endocrinol (Oxf)
Year:
2007
Document type:
Article
Affiliation country:
Brazil