SHOX Gene In The Short Stature Syndrome Of Children

The short stature is the most common endocrine disorder in pediatrics. three percent children suffer from this disease. Linear growth is a multifactorial trait that is influenced and regulated by a combination of environmental and internal factors. Among the intrinsic determinants of final body height, genetic factors have become more and more prominent, and the list of genes involved in growth-related processes has been extended accordingly. One of the most exciting additions to this list is represented by the discovery of the pseudoautosomal gene SHOX. Originally described as a gene responsible for idiopathic short stature, it has become clear that SHOX mutations can also cause mesomelic short stature and Madelung deformity in Leri-Weill syndrome. In addition, recent studies implicate SHOX haploinsufficiency in a variety of somatic Turner syndrome stigmata.Objective: To investigate the mutations of exon 3 of the SHOX gene in the children of short stature, to develop new diagnostic and therapeutic strategies to ensure adequate counselling and care for these patients.Methods: there were totally 30 short stature children investigated from the pediatrics endocrine out-patient department of Tianjin medical university general hospital during January to Novermber, 2006. 20 of the 30 patients, whose age range from 8.1 to 17.8, were male and the rest 10 were female patients, a ll the patients are short (height < -2 standard deviation scores (SDS)). 9 patients are under the third percentile of growth curve. All the patients have normal thyroid function, The bone ages were fall behind the normal children, normal CT of head. No chronic disease and mental disease.The normal control group from 25 healthy individuals (10 males and 15 females) ranging in age from 4 to 15 years whose height are normal.Total genomic DNA was extracted from peripheral blood, exon 3 of SHOX was amplified by polymerase chain reaction (PCR). PCR products obtained above were subjected to single-strand conformational polymorphism (SSCP) to detect mutations and confirmed with direct sequencing.Results: None mutation was identified in exon 3 of SHOX gene. One female patient was diagnosed of Turner syndrome. Her karyotype was 45, X/46, X, +mar(40%vs 60%). Two variations were detected, TCG→TCT in codon 106 and C→G variation leading to CGC→CGG in codon 121. The patient was compound homozygous mutations but not induce changes of amino acids.Conclusions: 1 PCR-SSCP technique and DNA sequencing were credible in clarification of the molecular defects of the short stature. 2 None mutation was identified in exon 3 of SHOX gene by SSCP. 3 Two variations were detected in the TS patient :TCG→TCT in codon 106 and C→G variation leading to CGC→CGG in codon 121. the relationship between this variation and the patients' karyotype will be research further.