title: Variations in the high-mobility group-A2 gene (HMGA2) are associated with idiopathic short stature.
abstract: BACKGROUND
  Several association studies confirmed high-mobility group-A2 gene (HMGA2) polymorphisms as the most relevant variants contributing to height variability. Animal models and deletions in humans suggest that alterations of HMGA2 might be relevant in causing short stature. Together, these observations led us to investigate the involvement of HMGA2 in idiopathic short stature (ISS) through an association study and a mutation screening.
  
  
  METHODS
  We conducted an association study (155 ISS patients and 318 normal stature controls) with three HMGA2 single-nucleotide polymorphisms (SNPs) (SNPs rs1042725, rs7968682, and rs7968902) using a TaqMan-based assay. The patients were then analyzed by direct sequencing and multiplex ligation-dependent probe amplification (MLPA) to detect point mutations and genomic micro-rearrangements.
  
  
  RESULTS
  Considering a recessive model, an OR value >1 was observed for genotypes rs7968682 TT (Odds ratio (OR) = 1.72, confidence interval (CI): 1.14-2.58) and rs1042725 TT (OR = 1.51, CI: 1.00-2.28) in accordance to the effect exhibited by the single alleles in the general population. None of the patients carried possibly causative HMGA2 mutations.
  
  
  CONCLUSIONS
  Besides the already known role in determining variability in human height, HMGA2 polymorphisms also contribute to susceptibility to ISS. Moreover, we here report the first mutation screening performed in ISS concluding that HMGA2 has not a significant impact on the monogenic form of ISS.
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Ileana
authors.initials: I
authors.lastname: Fusco
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Deepak
authors.initials: D
authors.lastname: Babu
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Mellone
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Barizzone
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Paediatrics Unit, Novara, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fanelli
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Muniswamy
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Paediatrics Unit, Novara, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Petri
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Paediatrics Unit, Novara, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bellone
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Paediatrics Unit, Novara, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
authors.affiliation: Department of Health Sciences, Laboratory of Human Genetics, University of Eastern Piedmont, Novara and IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.
authors.forename: Mara
authors.initials: M
authors.lastname: Giordano
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D005787:Gene Frequency; D015321:Gene Rearrangement; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D025743:HMGA2 Protein / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D016017:Odds Ratio; D010641:Phenotype; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D020413:3' Untranslated Regions; D025743:HMGA2 Protein