title: SHOX intragenic microsatellite analysis in patients with short stature.
abstract: BACKGROUND
  SHOX haplo-insufficiency is considered the molecular basis of short stature in patients with Turner's syndrome, and gives rise to the short stature with mesomelic dysplasia and Madelung deformity of patients with Leri-Weill syndrome.
  
  
  OBJECTIVE
  Analysis of the intragenic SHOX microsatellite to define its utility in detecting SHOX haplo-insufficiency in patients with short stature.
  
  
  METHODS
  207 patients with short stature (57 girls with Turner's syndrome [TS] [24 mosaicisms]; 73 children with isolated short stature [ISS]; 77 patients with short stature and skeletal disproportion) and 30 control subjects. DNA extraction and PCR amplification of the intragenic SHOX microsatellite, at the 5'-untranslated region. SSCP and partial sequencing of the SHOX gene in one patient with Madelung deformity and two SHOX alleles. DXS1055 (Xp) and DXS1192 (Xq) microsatellites were also analyzed, together with DXS233 and DXS234 at 0 and 2 cM of the pseudoautosomal region (PAR), in patients with one SHOX allele.
  
  
  RESULTS
  1. 93% of patients with TS had a single SHOX allele, and allele unbalance was detected in the remainder. 2. Patients with ISS were not different from the normal population with respect to SHOX heterozygosity (0.92 and 0.93, respectively; p = 0.997). 3. Patients with short stature and skeletal disproportion showed a higher frequency of SHOX homo/hemizygosity (0.27 vs 0.08; p = 0.027). 4. Five patients with short stature with SHOX haplo-insufficiency were detected: three had Madelung deformity (inherited Yq;Xp translocation, de novo PAR deletion, and SHOX microdeletion), and two had de novo/inherited Xp partial monosomy.
  
  
  CONCLUSIONS
  The SHOX intragenic microsatellite might be a useful molecular marker to detect TS (including Xp distal deletions). SHOX haplo-insufficiency seems not to be an important contributor to ISS, but when skeletal disproportion is associated with short stature, a significant proportion of patients is found to have a single SHOX allele. Some of these patients were found to be SHOX haplo-insufficient upon molecular, cytogenetic and radiological examination.
authors.affiliation: Servicio de Bioquímica, Hospital La Paz, Madrid, Spain. bezqzieta@airtel.net
authors.forename: Begoña
authors.initials: B
authors.lastname: Ezquieta
authors.forename: Elena
authors.initials: E
authors.lastname: Cueva
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gracia
mesh_terms: D020121:5' Untranslated Regions; D000483:Alleles; D001827:Body Height / Q000235:genetics*; D001848:Bone Diseases, Developmental / Q000000981:diagnostic imaging / Q000235:genetics; D002648:Child; D005260:Female; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007621:Karyotyping; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011859:Radiography; D017422:Sequence Analysis, DNA; D000074122:Short Stature Homeobox Protein; D014178:Translocation, Genetic; D014424:Turner Syndrome / Q000235:genetics
chemical_list: D020121:5' Untranslated Regions; D018398:Homeodomain Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein